Actinic Keratosis Pathogenesis Update and New Patents.

PubMed

Cantisani, Carmen; Paolino, Giovanni; Melis, Marcello; Faina, Valentina; Romaniello, Federico; Didona, Dario; Cardone, Michele; Calvieri, Stefano

2016-01-01

Actinic keratosis is a common premalignant skin lesion. Because of its increasing incidence, several efforts have been made to earlier detectection and to improve knowledge on photocarcinogenic pathways of keratinocytes. As a consequence, recently new discoveries have been done in this field. Starting from our previous review on actinic keratosis, we reviewed the literature focusing on pathogenesis and new patents in order to highlight the most recent progresses in diagnosis and therapeutic approach. Although several efforts have been done in the field of photodamaged skin, new upgrades in diagnosis and therapy are needed to detect superficial actinic keratosis earlier, to improve the disease free survival of patient and to better treat the field cancerization.

Topical Imiquimod in the Treatment of Conjunctival Actinic Keratosis.

PubMed

Rowlands, Megan A; Giacometti, Joseph N; Servat, Javier; Materin, Miguel A; Levin, Flora

Conjunctival actinic keratosis is rare and difficult to treat, as recurrences are common. Imiquimod, an immune response modulator, is currently Food and Drug Administration-approved for cutaneous actinic keratosis and superficial basal cell carcinomas. Emerging reports have shown it to be effective in treating some periocular and conjunctival lesions. The authors present a case of a 68-year-old white man with recurrent actinic keratosis involving the pretarsal conjunctiva, which was successfully treated with 5% topical imiquimod following previous failure with cryotherapy and interferon α-2b. The patient had ocular irritation that resolved on cessation of treatment. To the authors' knowledge, this is the first report of conjunctival actinic keratosis being treated with and successfully eradicated by topical imiquimod.

Oral acetylsalicylic acid and prevalence of actinic keratosis.

PubMed

Schmitt, Juliano; Miot, Hélio

2014-01-01

To investigate the influence of a regular oral use of acetylsalicylic acid in the prevalence of actinic keratosis. A case-control study with dermatologic outpatients above 50 years of age assessed between 2009 and 2011. Cases were defined as those who had been under regular use of oral acetylsalicylic acid for more than six consecutive months. The assessment focused on: age, sex, skin-type, tobacco smoking, use of medication, occurrence of individual or family skin cancer, and sunscreen and sun exposure habits. Actinic keratoses were counted in the medial region of the face and upper limbs. Counts were adjusted by co-variables based on a generalized linear model. A total of 74 cases and 216 controls were assessed. The median time of acetylsalicylic acid use was 36 months. Cases differed from controls as to the highest age, highest prevalence of use of angiotensin-converting enzyme inhibitors and fewer keratosis on the face and on the upper limbs (p<0.05). The multivariate model showed that the use of acetylsalicylic acid was associated to lower counts of face actinic keratosis and upper-limb erythematous actinic keratosis (p<0.05), regardless of other risk factors. The regular use of oral acetylsalicylic acid for more than six months was associated to a lower prevalence of actinic keratosis, especially facial and erythematous ones.

Actinic keratosis-related signs predictive of squamous cell carcinoma in renal transplant recipients: a nested case-control study.

PubMed

Jiyad, Z; O'Rourke, P; Soyer, H P; Green, A C

2017-04-01

Squamous cell carcinoma (SCC) and intraepidermal carcinoma (IEC) commonly arise in actinically damaged skin. To identify clinical features of actinic change that correlate with an increased risk of SCC or IEC in the short-to-medium term as guidance for prioritizing field treatment. In a nested case-control study, cases were renal transplant recipients who developed an incident SCC or IEC within 18 months following baseline examination and photography. Controls without SCC or IEC were matched to cases on age, sex and duration of immunosuppression. Predefined skin sites on the head, neck and upper limbs were examined using baseline photographs to assess objectively the following features of actinic damage: presence of actinic keratosis (AK) patch (defined as AK > 1 cm 2 ), number of AK patches, number of AKs and area affected by AK. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using McNemar's test to identify differences in SCC/IEC risk combined and SCC risk alone between case and control skin sites. Thirty-nine cases were matched to 39 controls. Significant associations with the presence of an AK patch, number of AK patches, number of AKs and area affected by AKs were identified. The presence of an AK patch conferred an 18-fold increased risk of SCC (OR 18·00, 95% CI 2·84-750) and more than a sixfold increased risk of SCC/IEC combined (OR 6·60, 95% CI 2·56-21·66). AK patches are predictive of SCC/IEC development within 18 months. This can be used to guide site selection for field treatment in patients with widespread actinic damage. © 2016 British Association of Dermatologists.

CD40 Ligand Is Increased in Mast Cells in Psoriasis and Actinic Keratosis but Less So in Epithelial Skin Carcinomas.

PubMed

Haimakainen, Salla; Kaukinen, Antti P; Suttle, Mireille-Maria; Pelkonen, Jukka; Harvima, Ilkka T

2017-03-16

The expression of CD40 ligand (CD40L) in mast cells was investigated in biopsies from lesional and non-lesional skin samples of patients with psoriasis, actinic keratosis (AK), basal cell carcinoma, and squamous cell carcinoma using a sequential double-staining technique. The percentage of CD40L + mast cells was higher in the lesional than in the non-lesional skin (p < .003). Interestingly, this percentage was lower in both carcinomas than in psoriasis and actinic keratosis (p < .025). Cells immunopositive for CD40 receptor were increased in all lesion types but especially so in carcinomas. The results suggest a dysregulated anti-tumoral immune response by mast cell CD40L in skin carcinomas.

Liquid nitrogen for the treatment of actinic keratosis: a longitudinal assessment.

PubMed

Ianhez, Mayra; Miot, Hélio Amante; Bagatin, Edileia

2014-08-01

Cryosurgery with liquid nitrogen is one of the most used treatments for actinic keratosis. We aimed to study the effectiveness of two consecutive sessions of cryosurgery for actinic keratosis and investigate factors associated with its therapeutic success. Hence, we conducted a longitudinal study including 92 patients of both sexes, aged 50-75 years with 5-50 actinic keratosis on the face and forearms, who underwent cryosurgery and treatment with sunscreen SPF 30, at baseline and after 120 days. The lesions were counted in duplicate by the same examiner before the start of treatment and after 120 (N=92) and 300 days (N=33), represented by their medians and quartiles and compared using the generalized linear mixed effects model (negative binomial). Treatment behavior was investigated in relation to sex, age, education, skin type, smoking, sun exposure at work and the use of aspirin, anti-inflammatory and angiotensin-converting enzyme inhibitors. There was a significant reduction in the actinic keratosis count on the face and forearms (p<0.05). Our results confirmed the effectiveness of cryosurgery for actinic keratosis, with a 57% reduction in the number, and size of the lesions. Higher education levels (p=0.02) and less sun exposure at work (p=0.02) independently promoted a significant reduction in the actinic keratosis count. Different population groups showed characteristic responses to the treatment, which may be explained by the degree of adherence to the use of photoprotection. In two sessions, cryosurgery with liquid nitrogen reduced the actinic keratosis count. Copyright © 2014 Elsevier Inc. All rights reserved.

Is imiquimod effective and safe for actinic keratosis?

PubMed

Walker, J Kendall; Koenig, Clint

2003-03-01

Imiquimod 5% cream, applied 3 times per week for 12 weeks, is effective for treatment of actinic keratosis. Severe erythema and other local reactions occurred in almost everyone receiving treatment, due to imiquimod's immune system-modulating effects. The 25 patients in the treatment group tolerated these adverse effects well. Despite these effects, imiquimod can be used as an alternative to traditional cryotherapy for the treatment of actinic keratosis among selected, motivated

Cost for the treatment of actinic keratosis on the rise in Australia

PubMed Central

Perera, Eshini; McGuigan, Sean; Sinclair, Rodney

2014-01-01

Objectives: To report the burden and cost of actinic keratosis (AK) treatment in Australia and to forecast the number of AK treatments and the associated costs to 2020. Design and setting: A retrospective study of data obtained from medicare Australia for AK treated by cryotherapy between 1 January 1994 and 31 December 2012, by year and by state or territory. Results: The total number of AK cryotherapy treatments increased from 247,515 in 1994 to 643,622 in 2012, and we estimate that the number of treatments will increase to 831,952 (95% CI 676,919 to 986,987) by 2020. The total Medicare Benefits Schedule (MBS) benefits paid out for AK in 2012 was $19.6 million and we forecast that this will increase to $24.7 million by 2020 (without inflation). Conclusion: The number of AK cryotherapy treatments increased by 160% between 1994 and 2012. we forecast that the number of treatments will increase by 30% between 2012 and 2020. The rates of non-melanoma skin cancer (NMSC) and AK appear to be increasing at the same rate. During the period 2010 to 2015 AK is anticipated to increase by 17.8% which follows a similar trend to published data that forecasts an increase in NMSC treatments of 22.3%. PMID:25309734

Physicians' opinions and clinical practice patterns for actinic keratosis management in Italy.

PubMed

Peris, K; Neri, L; Calzavara Pinton, P; Catricalà, C; Pellacani, G; Pimpinelli, N; Peserico, A

2014-04-01

We report dermatologists' opinions and clinical practice patterns about clinical factors driving decision making in the management of actinic keratosis (AK) in Italy. We carried out a cross-sectional survey among 33 Italian dermatologists. Physicians were asked to report their management choices in consecutive patients with AK seen at their practice within 2 weeks since study initiation. We collected patients' clinical and socio-demographic characteristics with a standardized data collection form and assessed physicians' opinions on AK management with a self-reported questionnaire. Six hundred fifty-seven patients with new, single AK lesions without evidence of photo-damaged skin in the surrounding areas, were predominantly treated with lesion-directed therapies (primarily cryotherapy). In contrast, physicians preferentially prescribed field-directed therapies to patients with multiple lesions and evidence of photo-damaged skin in AK surrounding areas. However we observed a wide variation in treatment choices and physicians' opinions on AK management. Dermatologists underlined the importance of fostering patients' adherence and minimize therapy side effects. Overall, our results show that current guidelines regarding management of AK are only partially integrated in dermatology practice. The active dissemination of up-to-date national guidelines might help harmonize clinical decision making in this complex and fast growing therapeutic area.

Pharmacoeconomic Considerations in Treating Actinic Keratosis: An Update.

PubMed

Vale, Spencer M; Hill, Dane; Feldman, Steven R

2017-02-01

Actinic keratosis is one of the most common dermatological diagnoses worldwide, especially among the elderly, fair-skinned, and immunocompromised, and is associated with a risk of transformation to skin cancer. With actinic keratosis and skin cancer prevalence increasing as the aged population expands in the US, optimizing treatment strategies may produce cost savings for the healthcare system. Since the time of our last review in 2008, investigation of the economic considerations in treating actinic keratosis has advanced. To provide an update of treatment cost effectiveness and to review factors relating to the costs of care, we conducted a systematic review of pharmacoeconomic publications since December 2008. We identified 11 pharmacoeconomic studies, with one cost-of-treatment, five cost-effectiveness, and five cost-utility analyses. Photodynamic therapy (PDT) was well tolerated and produced a favorable cosmetic outcome in most studies. Ingenol mebutate, the newest but most expensive topical field therapy, 5-fluorouracil, and PDT were the most cost-effective treatments in our review. Patient adherence to therapy and the management of adverse effects were significant contributors to treatment costs. In the US, treatment guidelines and formalized cost-effectiveness analyses for actinic keratosis are absent from the recent literature. Future pharmacoeconomic investigation will depend on up-to-date comparative efficacy data, as well as clarification of rates of, and management strategies for, adverse effects, therapeutic non-adherence, and lesion recurrence.

Laser-mediated Photodynamic Therapy: An Alternative Treatment for Actinic Keratosis?

PubMed

Kessels, Janneke P H M; Nelemans, Patty J; Mosterd, Klara; Kelleners-Smeets, Nicole W J; Krekels, Gertruud A M; Ostertag, Judith U

2016-03-01

Photodynamic therapy (PDT) with light emitting diode (LED) illumination is a frequently used treatment modality for actinic keratosis (AK) with excellent cosmetic outcome. A major disadvantage, however, is the high pain score. Pulsed dye laser (PDL) illumination has been suggested, but the long-term efficacy of this treatment is unknown. In this split-face study we prospectively treated 61 patients with AK, with both LED-PDT and PDL-PDT. The mean change in the number of lesions between the end of follow-up and start of therapy was -4.25 (95% confidence interval (95% CI) -5.07; -3.43) for LED-PDT and -3.88 (95% CI -4,76; -2.99) for PDL-PDT, with a non-significant difference (p = 0.258) of -0.46 (95% CI -1.28; 0.35). The percentage decrease from baseline in the total number of AK was 55.8% and 47.8%, respectively, at 12-month follow-up. Visual analogue scale pain score was lower after PDL (mean 2.64) compared with LED illumination (mean 6.47). These findings indicate that PDL-PDT is an effective alternative illumination source fo.

Topical photodynamic therapy of actinic keratosis in renal transplant recipients.

PubMed

Piaserico, S; Belloni Fortina, A; Rigotti, P; Rossi, B; Baldan, N; Alaibac, M; Marchini, F

2007-01-01

Organ transplant recipients (OTRs) show an increased risk of precancerous (mostly actinic keratosis [AK]) and cancerous (mostly squamous cell carcinomas [SCC] and basal cell carcinomas [BCC]) cutaneous lesions. Their frequency increases with time after transplantation. AKs seem to progress more often and faster to invasive SCC in OTRs compared with the general population. The steady increase of risk of cutaneous premalignancies and malignancies with time after transplantation is an alarming figure because the number of organ allograft recipients who live for many years after transplantion is rapidly growing. This points out the need to devote more resources to skin cancer prevention, detection, and management. Various therapies, including cryotherapy, topical 5-fluorouracil, imiquimod, topical diclofenac, curettage, electrosurgery, carbon dioxide laser, and surgical excision, are available for AKs. However, most of these are limited by frequent relapses and the presence of multiple lesions over a wide area. Topical photodynamic therapy (PDT) represents an innovative therapeutic approach for nonsurgical treatment of cutaneous precancerous lesions and skin cancers. In this study we confirmed the usefulness of PDT in the treatment of AKs in OTRs, even in lesions relapsing or unresponsive to conventional treatment. We showed a complete response rate of 71%, after 2 treatments sessions that were 2 weeks apart. The response rate of scalp/facial lesions (72%) was higher compared with acral lesions (40%). Topical PDT could represent a useful therapeutic alternative for AKs in OTRs because large lesions can be treated with excellent cosmetic outcome.

Protein expression of MMP-2 and MT1-MMP in actinic keratosis, squamous cell carcinoma of the skin, and basal cell carcinoma.

PubMed

de Oliveira Poswar, Fabiano; de Carvalho Fraga, Carlos Alberto; Gomes, Emisael Stênio Batista; Farias, Lucyana Conceição; Souza, Linton Wallis Figueiredo; Santos, Sérgio Henrique Souza; Gomez, Ricardo Santiago; de-Paula, Alfredo Maurício Batista; Guimarães, André Luiz Sena

2015-02-01

Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are 2 skin neoplasms with distinct potentials to invasion and metastasis. Actinic keratosis (AK) is a precursor lesion of SCC. Immunohistochemistry was performed to evaluate the expression of MMP-2 and MT1-MMP in samples of BCC (n = 29), SCC (n = 12), and AK (n = 13). The ratio of positive cells to total cells was used to quantify the staining. Statistical significance was considered under the level P < .05. We found a higher expression of MMP-2 in tumor stroma and parenchyma of SCC as compared to BCC. The expression of this protein was also similar between SCC and its precursor actinic keratosis, and it was higher in the stroma of high-risk BCC when compared to low-risk BCC. MT1-MMP, which is an activator of MMP-2, was similarly expressed in all groups. Our results suggest that MMP-2 expression may contribute to the distinct invasive patterns seen in SCC and BCC. © The Author(s) 2014.

Quantitative fluorescence in situ hybridization measurement of telomere length in skin with/without sun exposure or actinic keratosis.

PubMed

Ikeda, Hiroyuki; Aida, Junko; Hatamochi, Atsushi; Hamasaki, Yoichiro; Izumiyama-Shimomura, Naotaka; Nakamura, Ken-Ichi; Ishikawa, Naoshi; Poon, Steven S; Fujiwara, Mutsunori; Tomita, Ken-Ichiro; Hiraishi, Naoki; Kuroiwa, Mie; Matsuura, Masaaki; Sanada, Yukihiro; Kawano, Youichi; Arai, Tomio; Takubo, Kaiyo

2014-03-01

Chromosomal and genomic instability due to telomere dysfunction is known to play an important role in carcinogenesis. To study telomere shortening in the epidermis surrounding actinic keratosis, we measured telomere lengths of basal, parabasal, and suprabasal cells in epidermis with actinic keratosis (actinic keratosis group, n = 18) and without actinic keratosis (sun-protected, n = 15, and sun-exposed, n = 13 groups) and in actinic keratosis itself as well as in dermal fibroblasts in the 3 groups, using quantitative fluorescence in situ hybridization. Among the 3 cell types, telomeres of basal cells were not always the longest, suggesting that tissue stem cells are not necessarily located among basal cells. Telomeres of basal cells in the sun-exposed group were shorter than those in the sun-protected group. Telomeres in the background of actinic keratosis and in actinic keratosis itself and those of fibroblasts in actinic keratosis were significantly shorter than those in the controls. Our findings demonstrate that sun exposure induces telomere shortening and that actinic keratosis arises from epidermis with shorter telomeres despite the absence of any histologic atypia. © 2014.

Predisposing factors of actinic keratosis in a North-West German population.

PubMed

Hensen, Peter; Müller, Marcel L; Haschemi, Ramin; Ständer, Hartmut; Luger, Thomas A; Sunderkötter, Cord; Schiller, Meinhard

2009-01-01

The growing incident rates of skin cancer and their corresponding precursor lesions, e.g. actinic keratosis (AK), among Caucasians have become an important public health problem. A multicenter case-control study was conducted to identify the risk factors of AK of a prototypical Central European population. The study population comprised a total of 331 cases and 383 controls. Using multivariate analysis we identified ten independent variables predicting the AK risk. The five most crucial were age (OR 1.11; 95% CI 1.08-1,14), gender (OR 3.92; 95% CI 2.42-6.36), history of previous skin malignancies (OR 6.47; 95% CI 3.21-13.03), pale skin phototype (OR 2.5; 95% CI 1.53-4.06), and sun exposure for occupational reasons (OR 1.72; 95% CI 1.01-2.92). Additionally, sun exposure for recreational reasons, denial of the use of sunscreens, painful sunburn episodes before the age of 20, and a familial history of skin malignancies are also significant independent correlates of AK. Our epidemiological data suggest that constitutional susceptibility and sunlight exposure are equally involved in the onset of AK. Additional prophylactic and educational efforts should focus on increasing sun protection policies and educational programs especially aimed at outdoor workers, men, fair skinned individuals and patients with a history of previous skin malignancies. These measures should be able to reduce the excessive incidence rates of AK among Caucasians in Central Europe.

Three-day Field Treatment with Ingenol Disoxate (LEO 43204) for Actinic Keratosis

PubMed Central

Tyring, Stephen; Nahm, Walter K.; Østerdal, Marie Louise; Petersen, Astrid H.; Berman, Brian

2017-01-01

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of ingenol disoxate gel using a once-daily, three-day field treatment regimen in patients with actinic keratosis. DESIGN: This was a Phase II, multicenter, open-label trial (clinicaltrials.gov: NCT02305888). SETTING: The study was conducted in 20 trial sites in the United States. PARTICIPANTS: Participants included patients with 5 to 20 clinically typical actinic keratosis lesions on the full face/chest (250cm2), scalp (25–250cm2), or the trunk/extremities (250cm2). MEASUREMENTS: We measured incidence of dose-limiting events based on local skin responses. Percentage reduction in actinic keratosis lesion count from baseline, complete clearance, and partial clearance (≥75%) of actinic keratosis lesions were assessed at Week 8. RESULTS: Nine of 63 (14.3%) patients in the face/chest group reported dose-limiting events; zero of 63 patients in the scalp group reported dose-limiting events; and 11 of 62 (17.7%) patients in the trunk/extremities group reported dose-limiting events. Mean composite local skin response scores peaked at Day 4, then rapidly declined, reaching or approaching baseline levels by Week 4. Less than five percent of patients reported severe adverse events; the most common treatment-related adverse events were application site pain and pruritus. The reduction in actinic keratosis lesion count was 78.9, 76.3, and 69.1 percent for the face/chest, scalp, and trunk/extremities groups, respectively. Complete clearance was achieved in 36.5, 39.7, and 22.6 percent of patients in the face/chest, scalp, and trunk/extremities groups, respectively. Partial clearance was achieved in 71.4, 65.1, and 50.0 percent of patients in the face/chest, scalp, and trunk/extremities groups, respectively. CONCLUSION: Ingenol disoxate demonstrated adverse events and local skin reaction profiles similar to results seen in trials evaluating shorter two-day regimens and was effective in patients with

Defining the actinic keratosis field: a literature review and discussion.

PubMed

Figueras Nart, I; Cerio, R; Dirschka, T; Dréno, B; Lear, J T; Pellacani, G; Peris, K; Ruiz de Casas, A

2018-04-01

Despite the chronic and increasingly prevalent nature of actinic keratosis (AK) and existing evidence supporting assessment of the entire cancerization field during clinical management, a standardized definition of the AK field to aid in the understanding and characterization of the disease is lacking. The objective of this review was to present and appraise the available evidence describing the AK cancerization field, with the aim of determining a precise definition of the AK field in terms of its molecular (including genetic and immunological), histological and clinical characteristics. Eight European dermatologists collaborated to conduct a review and expert appraisal of articles detailing the characteristics of the AK field. Articles published in English before August 2016 were identified using PubMed and independently selected for further assessment according to predefined preliminary inclusion and exclusion criteria. In addition, a retrospective audit of patients with AK was performed to define the AK field in clinical terms. A total of 32 review articles and 47 original research articles provided evidence of sun-induced molecular (including genetic and immunological) and histological skin changes in the sun-exposed area affected by AK. However, the available literature was deemed insufficient to inform a clinical definition of the AK field. During the retrospective audit, visible signs of sun damage in 40 patients with AK were assessed. Telangiectasia, atrophy and pigmentation disorders emerged as 'reliable or very reliable' indicators of AK field based on expert opinion, whereas 'sand paper' was deemed a 'moderately reliable' indicator. This literature review has revealed a significant gap of evidence to inform a clinical definition of the AK field. Therefore, the authors instead propose a clinical definition of field cancerization based on the identification of visible signs of sun damage that are reliable indicators of field cancerization based on expert

Variation in the Cost of Managing Actinic Keratosis

PubMed Central

Gregory, Tanner; Liu, Guodong; Leslie, Douglas L.; Miller, Jeffrey J.

2017-01-01

Importance Actinic keratosis (AK), a skin growth induced by ultraviolet light exposure, requires chronic management because a small proportion can progress into squamous cell skin cancer. Spending for AK management was more than $1 billion in 2004. Investigating geographic variation in AK spending presents an opportunity to decrease waste or recoup excess spending. Objective To evaluate geographic variation in health care cost for management of AKs and the association with patient-related and health-related factors. Design, Setting, and Participants This retrospective cohort study was performed using data from the MarketScan medical claims database of 488 324 continuously enrolled members with 2 or more claims for AK. Data from January 1, 2008, to December 31, 2012, was used. Main Outcomes and Measures Annual costs of care were calculated for outpatient visits, AK destruction, and medications for AKs, and the total of these components. Costs were adjusted for inflation to 2014 US dollars. To display cost variation, we calculated the ratio of mean cost in the highest quintile (Q5) relative to the mean in the lowest quintile (Q1), or the Q5:Q1 ratio; Q5:Q1 ratios were adjusted based on age, sex, history of nonmelanoma skin cancer, US geographic region, and population density (metropolitan statistical area). Results Overall, data from 488 324 continuously enrolled members (mean [SD] age, 53.1 [7.5] years; 243 662 women) with 2 or more claims for AK were included. Overall, patients had 1 085 985 claims related to AK, and dermatologists accounted for 71.0% of claims. The 2-year total cost was $111.5 million, with $52.4 million in 2011 and $59.1 million in 2012. The unadjusted Q5:Q1 ratios for total annual cost per patient ranged from 9.49 to 15.10. Adjusted ratios ranged from 1.72 to 1.80. Conclusions and Relevance There is variation in AK management cost within and between regions. This is not fully explained by differences in patient characteristics such as

Clinical effect of imiquimod 5% cream in the treatment of actinic keratosis.

PubMed

Persaud, Andrea N; Shamuelova, Eleonora; Sherer, Daniel; Lou, Wendy; Singer, Giselle; Cervera, Christina; Lamba, Sumedha; Lebwohl, Mark G

2002-10-01

Actinic keratosis (AK) is the earliest clinical manifestation of squamous cell carcinoma. Metastatic SCC causes the majority of the 1300 to 2300 deaths attributed to nonmelanoma skin cancer in the United States each year. Recent studies have shown that intralesional administration of interferon can be used successfully in the treatment of AK. Imiquimod is an immune response modifier, currently approved for the treatment of genital warts. The topically applied immune response modifier acts by up-regulating interferon and other cytokines involved in the cell-mediated immune response at the site of application. The aim of this was to determine the efficacy and safety of imiquimod 5% cream for the treatment of AK. Twenty-two patients with AK lesions were treated with imiquimod 5% cream, initially at 3 times per week for 8 weeks, or until total clearance of lesions. Patients applied imiquimod to lesions on one side of the body and vehicle cream to the other side. A total of 17 patients who completed treatment were evaluated for number of lesions and adverse reactions before treatment and at weeks 2, 4, 6, and 8 after initiation of treatment. AK lesions were also assessed 4 and 8 weeks after treatment. A significant reduction in the average number of lesions per patient was observed for patients treated with imiquimod. The most frequent reactions to treatment were erythema, itching, and scabbing; however, all adverse events were mild to moderate. Imiquimod 5% cream may be a promising treatment for AK.

A consensus approach to improving patient adherence and persistence with topical treatment for actinic keratosis

PubMed Central

Stockfleth, Eggert; Peris, Ketty; Guillen, Carlos; Cerio, Rino; Basset-Seguin, Nicole; Foley, Peter; Sanches, José; Culshaw, Alex; Erntoft, Sandra; Lebwohl, Mark

2015-01-01

Background Topical therapy is important in the treatment of actinic keratosis, but guidance for improving adherence/persistence during topical therapy is still lacking. Objectives To utilize expert consensus to generate a list of recommendations to improve real-world efficacy when prescribing topical therapy for actinic keratosis. Methods An expert panel of eight dermatologists was convened to generate recommendations based on facilitated discussion and consensus generation using a modified Delphi session. The recommendations were ratified with the expert panel. Results Facilitated discussion generated 31 issues within five themes, which were prioritized using expert voting. Consensus was achieved on the importance of short and simple treatment regimens for maximizing patient compliance, physician awareness of the progression of actinic keratosis to squamous cell carcinoma, provision of appropriate patient information, and the use of effective communication strategies to educate physicians about actinic keratosis. Based on these key findings, eight recommendations were generated. Conclusions The recommendations will assist physicians when prescribing topical actinic keratosis therapy. Further research should focus on the types of patient outcomes that are influenced by the characteristics of topical field therapy. PMID:25865875

Light emitting fabric for photodynamic treatment of actinic keratosis

NASA Astrophysics Data System (ADS)

Thecua, E.; Vicentini, C.; Vignion, A.-S.; Lecomte, F.; Deleporte, P.; Mortier, L.; Szeimies, R.-M.; Mordon, S.

2017-02-01

The integration of optical fibers into flexible textile structures, by using knitting or weaving processes can allow the development of flexible light sources. The paper aims to present a new technology: Light Emitting Fabrics (LEF), which can be used for example for PDT of Actinic Keratosis in Dermatology. The predetermined macro-bending of optical fibers, led to a homogeneous side emission of light over the entire surface of the fabric. Tests showed that additional curvatures when applying the LEF on non-planar surfaces had no impact on light delivery and proved that LEF can adapt to the human morphology. The ability of the LEF, coupled with a 635nm LASER source, to deliver a homogeneous light to lesions is currently assessed in a clinical trial for the treatment of AK of the scalp by PDT. The low irradiance and progressive activation of the photosensitizer ensure a pain reduction, compared to discomfort levels experienced by patients during a conventional PDT session.

New Topical Treatment Options for Actinic Keratosis: A Systematic Review.

PubMed

Stockfleth, Eggert; Sibbring, Gillian C; Alarcon, Ivette

2016-01-01

This systematic review compared the relative efficacy of 5-fluorouracil 0.5% in salicylic acid 10% (5-FU/SA), ingenol mebutate (IMB) and imiquimod 2.5%/3.75% (IMI) for actinic keratosis on the face, forehead or scalp. Only 11 publications, relating to 7 randomised controlled trials, met inclusion criteria and it was only possible to compare the effect of all 3 treatments on complete clinical clearance, and the effect of 5-FU/SA and IMB on actinic keratosis recurrence rate. Despite a higher vehicle response rate for 5-FU/SA, complete clinical clearance was higher than IMB and IMI (55.4, 42.2, and 25.0-30.6/34.0-35.6%, [corrected] respectively). 5-FU/SA was also associated with lower actinic keratosis recurrence rate than IMB at 12 months post-treatment (32.7 vs. 53.9%). Although qualitative assessment suggested a numerical advantage of 5-FU/SA over IMB and IMI in terms of complete clinical clearance and sustained clearance, clinical data from longer term trials, with comparable outcome measures, are required to corroborate these findings.

Expression of matrix metalloproteinase-1, -2 and -3 in squamous cell carcinoma and actinic keratosis

PubMed Central

Tsukifuji, R; Tagawa, K; Hatamochi, A; Shinkai, H

1999-01-01

Matrix metalloproteinase (MMP) plays an important role in extracellular matrix degradation associated with cancer invasion. An expression of MMP-1 (interstitial collagenase), MMP-2 (72-kDa type IV collagenase) and MMP-3 (stromelysin-1) was investigated in squamous cell carcinoma (SCC) and its precancerous condition, actinic keratosis (AK), using in situ hybridization techniques. MMP-1 mRNA was detected in tumour cells and/or in stromal cells in all cases of SCC, four of six AKs adjacent to SCC and four of 16 AKs. MMP-2 and MMP-3 mRNAs were detected in SCC but not in AK. The expression of MMP-3 correlated to that of MMP-1 (P = 0.03) localized at the tumour mass and stroma of the invasive area, while MMP-2 mRNA was detected widely throughout the stroma independent of MMP-1 expression. Our results indicated that the expression of MMP-1, -2 and -3 showed different localization patterns, suggesting a unique role of each MMP in tumour progression. Moreover, MMP-1 expression could be an early event in the development of SCC, and AK demonstrating MMP-1 mRNA, might be in a more advanced dysplastic state, progressing to SCC. © 1999 Cancer Research Campaign PMID:10362121

A consensus approach to improving patient adherence and persistence with topical treatment for actinic keratosis.

PubMed

Stockfleth, Eggert; Peris, Ketty; Guillen, Carlos; Cerio, Rino; Basset-Seguin, Nicole; Foley, Peter; Sanches, José; Culshaw, Alex; Erntoft, Sandra; Lebwohl, Mark

2015-01-01

Topical therapy is important in the treatment of actinic keratosis, but guidance for improving adherence/persistence during topical therapy is still lacking. To utilize expert consensus to generate a list of recommendations to improve real-world efficacy when prescribing topical therapy for actinic keratosis. An expert panel of eight dermatologists was convened to generate recommendations based on facilitated discussion and consensus generation using a modified Delphi session. The recommendations were ratified with the expert panel. Facilitated discussion generated 31 issues within five themes, which were prioritized using expert voting. Consensus was achieved on the importance of short and simple treatment regimens for maximizing patient compliance, physician awareness of the progression of actinic keratosis to squamous cell carcinoma, provision of appropriate patient information, and the use of effective communication strategies to educate physicians about actinic keratosis. Based on these key findings, eight recommendations were generated. The recommendations will assist physicians when prescribing topical actinic keratosis therapy. Further research should focus on the types of patient outcomes that are influenced by the characteristics of topical field therapy. © 2015 The Authors. International Journal of Dermatology published by John Wiley & Sons Ltd on behalf of International Society of Dermatology.

Ingenol mebutate in low amounts for the treatment of actinic keratosis in Korean patients.

PubMed

Joe, Hyun Jae; Oh, Byung Ho

2017-01-01

Ingenol mebutate (IM), a novel agent for field therapy of actinic keratosis (AK), has a drawback of inducing local skin reactions (LSRs), which may cause discomfort in patients. To reduce the LSRs, we tried the application of IM in low amounts. The purpose of this study was to review Korean patients with AK being treated with IM and evaluate the LSRs and therapeutic outcomes of low amounts of IM. We retrospectively reviewed 47 patients with AK on the face. A total of 20 and 27 patients were treated by applying recommended amount of 18.8 mg/cm 2 and the lower amount of 10 mg/cm 2 , respectively. The mean composite LSR score for the low amount group (LAG; 12.18±3.29) was significantly lower than that for the recommended amount group (RAG; 15.45±2.70) ( P <0.01, independent sample t -test). The 2-month clearance rate calculated by the number of AKs before and after treatment in each patient was significantly higher for RAG (88.16%), compared with 75.56% for LAG ( P <0.001). Low amount of IM for the treatment of facial AK significantly reduced LSRs in Korean patients. Minimizing LSRs may allow for a secondary targeting treatment of IM for the residual lesions, depending on initial treatment outcomes.

Actinic keratosis and diabetes complications: A nationwide population-based study in South Korea (2009-2015).

PubMed

Lee, YoungBok; Lee, JiHyun; Choi, JinYoung; Yu, DongSoo; Han, KyungDo; Park, Yong-Gyu

2017-11-29

As the associations between actinic keratosis (AK) and diabetes complications in patients with diabetes mellitus (DM) have never been investigated, this study aimed to evaluate any such associations in patients with DM. This retrospective cohort study analyzed clinical data for DM patients aged>40 years who had undergone the health examination recommended by the South Korea National Health Insurance Program between 2009 and 2012 (n=2,056,580). All of these patients were classified according to the presence of diabetic retinopathy (DR), end-stage renal disease (ESRD) and history of DVD; myocardial infarction, stroke, transient ischaemic attacks. Newly diagnosed AK was identified using claims data from baseline to the date of diagnosis or 31 December 2015, whichever came first. Of the 2,056,580 patients with DM, 6404 (0.31%) developed AK. Those patients in the DR, ESRD and CVD groups were more likely to be diagnosed with AK (P<0.001, by log-rank test). After adjusting for age and gender, the risks for AK were significantly higher in the DR, ESRD and CVD groups: HR (95% CI): 1.29 (1.21-1.39), HR: 4.24 (3.28-5.47) and HR: 1.22 (1.13-1.31), respectively. This study has revealed that the incidence of AK is higher in diabetes patients with ocular, renal and cardiovascular complications. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The current role of in vivo reflectance confocal microscopy within the continuum of actinic keratosis and squamous cell carcinoma: a systematic review.

PubMed

Nguyen, Kim P; Peppelman, Malou; Hoogedoorn, Lisa; Van Erp, Piet E J; Gerritsen, Marie-Jeanne P

2016-12-01

Clinical differentiation between actinic keratosis (AK), squamous cell carcinoma (SCC) in situ, and invasive SCC and its variants may be difficult. Reflectance confocal microscopy (RCM) is a non-invasive technique for in vivo skin imaging. To explicate the diagnostic and monitoring use of RCM within the spectrum of AK and SCC, and evaluate the accuracy of RCM for these diagnoses relative to histopathology. A systematic literature search was performed in PubMed, EMBASE, the Cochrane Library, and Web of Science databases. The quality was assessed using the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist. Twenty-five eligible studies were included. Different diagnostic RCM features have been described for AK, actinic cheilitis (AC), erythroplasia of Queyrat, Bowen disease, invasive SCC, and keratoacanthoma (KA). The overall range of sensitivity and specificity of RCM for the diagnosis of SCC, AK, SCC in situ, and KA was 79-100% and 78-100%, respectively. The current literature describes the use of RCM for diagnosing AK, AC, erythroplasia of Queyrat, Bowen disease, invasive SCC, and KA, as well as for monitoring treatments of AK, with good accuracy. Unfortunately, studies with high methodological quality are lacking. Pre-treatment of hyperkeratotic lesions and uniform definitions of RCM features are required to simplify the differentiation between AKs, SCC in situ, and SCC and its variants in clinical practice.

Photodynamic therapy in the management of actinic keratosis: Retrospective evaluation of outcome.

PubMed

Jerjes, Waseem; Hamdoon, Zaid; Abdulkareem, Ali A; Hopper, Colin

2017-03-01

Photodynamic therapy (PDT) is a minimally invasive intervention used in the management of tissue disorders. In this retrospective study, a total of 62 patients with actinic keratosis (AKs) were treated with surface illumination PDT. Comparisons with the clinical features, rate of recurrence as well as malignant transformation and overall outcome were made. The medical records of 62 consecutive patients who presented with suspicious skin lesions and diagnosed with AKs were examined. These patients with 178 AKs lesions were treated with surface illumination methyl aminolevulinate-photodynamic therapy (MAL-PDT). The 16% strength cream (MAL) was applied topically 3h prior to tissue illumination. A single-channel 628nm diode laser was used for illumination and light was delivered at 100J/cm 2 per site. These patients were followed-up for a mean of 7.4 years. Eight recurrences were reported after the first round of MAL-PDT, and two recurrences after the second round. Malignant transformation to squamous cell carcinoma (SCC) was noted in 2 patients only. The 3-year outcome resulted in 60 patients with complete response (CR), and this was maintained at the final outcome (last clinic review). Assessment of lesional outcome vs. response showed that 175/178 treated lesions had complete response (CR) at 3-year follow-up, which increased to 176/178 lesions at the last clinic follow-up. MAL-PDT offers an effective treatment for AKs lesions with excellent cosmetic outcome. Copyright © 2016 Elsevier B.V. All rights reserved.

Eyebrow hairs from actinic keratosis patients harbor the highest number of cutaneous human papillomaviruses

PubMed Central

2013-01-01

Background Cutaneous human papillomavirus (HPV) infections seem to be associated with the onset of actinic keratosis (AK). This study compares the presence of cutaneous HPV types in eyebrow hairs to those in tissues of normal skin and skin lesions of 75 immunocompetent AK patients. Methods Biopsies from AK lesions, normal skin and plucked eyebrow hairs were collected from each patient. DNA from these specimens was tested for the presence of 28 cutaneous HPV (betaPV and gammaPV) by a PCR based method. Results The highest number of HPV prevalence was detected in 84% of the eyebrow hairs (63/75, median 6 types) compared to 47% of AK lesions (35/75, median 3 types) (p< 0.001) and 37% of normal skin (28/75, median 4 types) (p< 0.001), respectively. A total of 228 HPV infections were found in eyebrow hairs compared to only 92 HPV infections in AK and 69 in normal skin. In all three specimens HPV20, HPV23 and/or HPV37 were the most prevalent types. The highest number of multiple types of HPV positive specimens was found in 76% of the eyebrow hairs compared to 60% in AK and 57% in normal skin. The concordance of at least one HPV type in virus positive specimens was 81% (three specimens) and 88-93% of all three combinations with two specimens. Conclusions Thus, eyebrow hairs revealed the highest number of cutaneous HPV infections, are easy to collect and are an appropriate screening tool in order to identify a possible association of HPV and AK. PMID:23618013

Eyebrow hairs from actinic keratosis patients harbor the highest number of cutaneous human papillomaviruses.

PubMed

Schneider, Ines; Lehmann, Mandy D; Kogosov, Vlada; Stockfleth, Eggert; Nindl, Ingo

2013-04-24

Cutaneous human papillomavirus (HPV) infections seem to be associated with the onset of actinic keratosis (AK). This study compares the presence of cutaneous HPV types in eyebrow hairs to those in tissues of normal skin and skin lesions of 75 immunocompetent AK patients. Biopsies from AK lesions, normal skin and plucked eyebrow hairs were collected from each patient. DNA from these specimens was tested for the presence of 28 cutaneous HPV (betaPV and gammaPV) by a PCR based method. The highest number of HPV prevalence was detected in 84% of the eyebrow hairs (63/75, median 6 types) compared to 47% of AK lesions (35/75, median 3 types) (p< 0.001) and 37% of normal skin (28/75, median 4 types) (p< 0.001), respectively. A total of 228 HPV infections were found in eyebrow hairs compared to only 92 HPV infections in AK and 69 in normal skin. In all three specimens HPV20, HPV23 and/or HPV37 were the most prevalent types. The highest number of multiple types of HPV positive specimens was found in 76% of the eyebrow hairs compared to 60% in AK and 57% in normal skin. The concordance of at least one HPV type in virus positive specimens was 81% (three specimens) and 88-93% of all three combinations with two specimens. Thus, eyebrow hairs revealed the highest number of cutaneous HPV infections, are easy to collect and are an appropriate screening tool in order to identify a possible association of HPV and AK.

Optical coherence tomography in the diagnosis of actinic keratosis-A systematic review.

PubMed

Friis, K B E; Themstrup, L; Jemec, G B E

2017-06-01

Optical coherence tomography (OCT) is a real-time non-invasive imaging tool, introduced in dermatology in the late 1990s. OCT uses near-infrared light impulses to produce images which can be displayed in cross-sectional and en-face mode. The technique has been used to image skin diseases especially non-melanoma skin cancer including actinic keratosis (AK). Morphological characteristics of AK can be visualized in OCT images and can be used for diagnosis as well as disease monitoring. A systematic review of original papers on AK and OCT was performed on 31.03.16 and 24.10.16 in the major databases Pubmed, MEDLINE, EMBASE, Cochrane and Svemed. Through database search and other sources, we identified 1366 titles of which 21 studies met the inclusion criteria and were used for further investigation. 16/16 Conventional OCT (cross-sectional images) studies described disruption of layers consistent with absence of normal layered architecture in the skin. Thickened epidermis was found in 14/16 studies and white (hyperreflective) streaks and dots were described in 11/16 studies. In High-definition optical coherence tomography (HD-OCT) images disarranged epidermis (cross-sectional images) along with an atypical honeycomb pattern (en-face images) was found in 5/5 studies and well-demarcated dermo-epithelial junction (DEJ) (cross-sectional images) was described in 3/5 studies. Several morphological characteristics of AKs were identified using Conventional OCT and HD-OCT. It is suggested that these may be used in the diagnosis of AK. Additional validation is however required to establish consensus on the optimal diagnostic criteria. Copyright © 2017 Elsevier B.V. All rights reserved.

Quality of Life, Behaviour and Attitudes towards Actinic Keratosis in Spain: The PIQA Study.

PubMed

Longo, I; Serra-Guillén, C

2018-05-01

This study was aimed to examine patients' knowledge, behaviours and attitudes regarding actinic keratosis (AK) lesions and the impact of the disease on patients' quality of life (QoL). Observational study of patients with AK lesions in Spain. QoL was evaluated with the validated version of Spanish AKQoL questionnaire. Skin self-examination, sun-exposure, habits and attitudes towards AK's treatment were recorded using different questionnaires. The adherence was assessed by means of the Morisky-Green test. Among other variables, QoL and adherence to treatment were compared by using Pearson's χ 2 test and one-way ANOVA tests. Inferential analysis regarding such factors and length of treatment were also performed. A total of 1240 patients (73.6 [10.5] years old) were recruited. Overall, patients that showed higher levels of concern were also showed a higher impairment on QoL. AK had greater effects on women's QoL and those who performed skin self-examination, think that AK is a disease and/or believe that moisturizers can prevent skin aging (P<.05). Adherence and length of treatment were strongly related, since patients with treatments intended for <1week were more likely to show good adherence and complete remission of AK (Odds Ratio [95%CI]: 6.25 [4.55-8.33] and 2.63 [1.96-3.45]), respectively). Concerns due to AK are mainly related to sex and to the consideration of AK as a disease. More concerned patients tend to have lower QoL and good adherence to treatment. Short length of treatment was associated with better adherence and complete remission of AK lesions. Copyright © 2018 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Three-day Field Treatment with Ingenol Disoxate (LEO 43204) for Actinic Keratosis: A Phase II Trial.

PubMed

Siegel, Daniel M; Tyring, Stephen; Nahm, Walter K; Østerdal, Marie Louise; Petersen, Astrid H; Berman, Brian

2017-12-01

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of ingenol disoxate gel using a once-daily, three-day field treatment regimen in patients with actinic keratosis. DESIGN: This was a Phase II, multicenter, open-label trial (clinicaltrials.gov: NCT02305888). SETTING: The study was conducted in 20 trial sites in the United States. PARTICIPANTS: Participants included patients with 5 to 20 clinically typical actinic keratosis lesions on the full face/chest (250cm 2 ), scalp (25-250cm 2 ), or the trunk/extremities (250cm 2 ). MEASUREMENTS: We measured incidence of dose-limiting events based on local skin responses. Percentage reduction in actinic keratosis lesion count from baseline, complete clearance, and partial clearance (≥75%) of actinic keratosis lesions were assessed at Week 8. RESULTS: Nine of 63 (14.3%) patients in the face/chest group reported dose-limiting events; zero of 63 patients in the scalp group reported dose-limiting events; and 11 of 62 (17.7%) patients in the trunk/extremities group reported dose-limiting events. Mean composite local skin response scores peaked at Day 4, then rapidly declined, reaching or approaching baseline levels by Week 4. Less than five percent of patients reported severe adverse events; the most common treatment-related adverse events were application site pain and pruritus. The reduction in actinic keratosis lesion count was 78.9, 76.3, and 69.1 percent for the face/chest, scalp, and trunk/extremities groups, respectively. Complete clearance was achieved in 36.5, 39.7, and 22.6 percent of patients in the face/chest, scalp, and trunk/extremities groups, respectively. Partial clearance was achieved in 71.4, 65.1, and 50.0 percent of patients in the face/chest, scalp, and trunk/extremities groups, respectively. CONCLUSION: Ingenol disoxate demonstrated adverse events and local skin reaction profiles similar to results seen in trials evaluating shorter two-day regimens and was effective in patients

Dermal changes in superficial basal cell carcinoma, melanoma in situ and actinic keratosis and their implications

PubMed Central

Kazlouskaya, Viktoryia; Malhotra, Saurabh; Navarro, Raquel; Wu, Karen Nguyen; Shvartsbeyn, Marianna; Shengli, Chen; Gui, Jiang; Elston, Dirk M.

2018-01-01

Background Basal cell carcinoma (BCC) has a characteristic stroma, but less is known about the dermal characteristics associated with melanoma in situ (MIS) and actinic keratosis (AK). Materials and methods Dermal changes were studied in 301 specimens of AK, BCC and MIS. Subsequently, blinded images of dermal changes from 90 randomly selected cases of those entities were used to assess the predictive value of the dermal changes. Agreement with the final diagnosis was calculated using kappa coefficient (κ). Results Fibromyxoid stroma was present in 82% of BCC cases; fibrous stroma was seen in 25% of BCC, 58% of MIS and 35.6% of AK specimens (p <0.05). A lichenoid inflammatory infiltrate was frequently associated with AK and a perifollicular infiltrate with periadnexal fibrosis with MIS. Blinded evaluation of images of the dermal changes associated with the tumors yielded the correct diagnosis in (54.4, 41.1 and 27.8%; average 41.2%) by the three appraisers. Coefficient of agreement in blinded imaged evaluation with the actual diagnosis was higher in the BCC and MIS compared with AK (κ = 0.37, p = 0.0001; κ = 0.2, p = 0.0005 and κ = −0.06, p = 0.84, respectively). Conclusion Dermal features may be helpful in predicting the correct diagnosis when tumor is not visible. PMID:24117926

Acantholytic squamous cell carcinoma is usually associated with hair follicles, not acantholytic actinic keratosis, and is not "high risk": Diagnosis, management, and clinical outcomes in a series of 115 cases.

PubMed

Ogawa, Toru; Kiuru, Maija; Konia, Thomas H; Fung, Maxwell A

2017-02-01

Acantholytic squamous cell carcinoma (aSCC) is regarded as a high-risk variant of cutaneous squamous cell carcinoma (SCC). Acantholytic actinic keratosis (aAK) has been regarded as a precursor risk factor for aSCC. However, supporting evidence is limited. We sought to document clinical features, histologic features, management, and outcomes in a series of aSCC cases. Definitions of aSCC, aAK, and aSCC arising in association with aAK were applied to a consecutive series of aSCC cases. Clinical characteristics and outcomes were obtained from electronic medical records. Of 115 aSCC cases (103 patients, mean age 71.8 years), actinic keratosis was present in 23% (27/115) but only 7.8% (9/115) exhibited associated aAK. Ten cases (10/115, 9%) fulfilled strict histologic criteria for follicular SCC as previously defined, but 50 of 115 (43%) of our aSCC cases exhibited predominant involvement of follicular epithelium rather than epidermis. Clinical outcome (median follow-up, 36 months) was available in 106 of 115 (92%). One patient experienced regional extension (parotid), and 1 patient experienced a local recurrence (nose). No disease-related metastases or deaths were documented. This was a single-institution retrospective study from the United States. The presence of acantholysis in cutaneous SCC does not specifically confer aggressive behavior, a finding that may inform clinical practice guidelines. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Atopic dermatitis is not associated with actinic keratosis: cross-sectional results from the Rotterdam study.

PubMed

Hajdarbegovic, E; Blom, H; Verkouteren, J A C; Hofman, A; Hollestein, L M; Nijsten, T

2016-07-01

Epidermal barrier impairment and an altered immune system in atopic dermatitis (AD) may predispose to ultraviolet-induced DNA damage. To study the association between AD and actinic keratosis (AK) in a population-based cross-sectional study. AD was defined by modified criteria of the U.K. working party's diagnostic criteria. AKs were diagnosed by physicians during a full-body skin examination, and keratinocyte cancers were identified via linkage to the national pathology database. The results were analysed in adjusted multivariable and multinomial models. A lower proportion of subjects with AD had AKs than those without AD: 16% vs. 24%, P = 0·002; unadjusted odds ratio (OR) 0·60, 95% confidence interval (CI) 0·42-0·83; adjusted OR 0·74, 95% CI 0·51-1·05; fully adjusted OR 0·69, 95% CI 0·47-1·07. In a multinomial model patients with AD were less likely to have ≥ 10 AKs (adjusted OR 0·28, 95% CI 0·09-0·90). No effect of AD on basal cell carcinoma or squamous cell carcinoma was found: adjusted OR 0·71, 95% CI 0·41-1·24 and adjusted OR 1·54, 95% CI 0·66-3·62, respectively. AD in community-dwelling patients is not associated with AK. © 2016 British Association of Dermatologists.

Rosettes in actinic keratosis and squamous cell carcinoma: distribution, association to other dermoscopic signs and description of the rosette pattern.

PubMed

Lozano-Masdemont, B; Polimón-Olabarrieta, I; Marinero-Escobedo, S; Gutiérrez-Pecharromán, A; Rodríguez-Lomba, E

2018-01-01

Rosettes, a dermoscopic structure characterized by four white points arranged as a 4-leaf clover, supports the dermoscopic diagnosis of actinic keratosis (AK) or squamous cell carcinoma (SCC). The association of rosettes with other dermoscopic structures in AK or SCC and their distribution has not been analysed yet. We conducted a prospective study of patients with histologically proven AK or SCC who presented dermoscopic rosettes at initial evaluation. A total of 56 tumours were collected (94.6% AK and 5.4% SCC). Thirty-seven (66.1%) lesions were non-pigmented and 19 (33.9%) pigmented. The most common dermoscopic findings were erythema (53; 94.6%) and scale (42; 75%). White circles were present in 21 lesions (37.5%); pigmented pseudonetwork in 18 (32.1%) and multiple grey to brown dots and globules in 14 (25%). Rosettes were distributed focally in 9 (16.1%) and generalized in 47 (83.9%). The rosette pattern (rosettes as the main structure) was observed only in AK (19; 35.8%). The analysis was not blinded. The distinction between focal distribution (up to 3 rosettes) or generalized could be considered arbitrary. The rosette pattern identified in AK may be a specific pattern for AK. © 2017 European Academy of Dermatology and Venereology.

Influence of Information Framing on Patient Decisions to Treat Actinic Keratosis.

PubMed

Berry, Katherine; Butt, Melissa; Kirby, Joslyn S

2017-05-01

Actinic keratosis (AK) is a skin growth induced by UV light exposure that requires long-term management because a small proportion of the disease can progress to squamous cell carcinoma. The influence of how clinicians frame or present information to patients may affect decision making about AK. To evaluate the differences in patients' decisions on whether to receive treatment for AK related to information presentation or choice framing. A prospective survey study was performed from June 1 to July 31, 2016, in participants who were able to read English. Participants were recruited through the Penn State Milton S. Hershey Dermatology Clinic and an online survey site. The survey was conducted through an online portal. A total of 571 individuals were recruited. Regression analysis, correlation coefficient analysis, and test-retest validation were conducted. The proportions of patients choosing to receive treatment for AK. Analyses were performed to adjust for age, sex, educational level, history of skin cancer, and history of AK. Of the 571 recruited participants, 539 (94.4%) returned completed surveys. The mean (SD) age of respondents was 42.9 (17.8) years; 306 (56.8%) were women. The decision to receive treatment for AK varied from 57.7% (n = 311) to 92.2% (n = 497) for the 5 scenarios presented in the questions (P < .001). The question that presented AK as a "precancer" had the highest proportion of participants who preferred treatment (497 [92.2%]). Two questions that presented the risk of AK as not progressing to cancer had the lowest proportion of individuals who chose treatment (311 [57.7%] and 328 [60.9%]). Participants from the clinic and from the online portal were significantly different in age (mean [SD] age, 56.1 [17.6] vs 33.3 [10.0] years), sex (145 [63.6%] vs 161 [51.8%] were females), educational level (40 [17.5%] vs 80 [25.7%] had completed some graduate school), history of AK (46 [20.2%] vs 19 [6.1%] answered yes), and history of skin

Electrospun poly-l-lactide scaffold for the controlled and targeted delivery of a synthetically obtained Diclofenac prodrug to treat actinic keratosis.

PubMed

Piccirillo, Germano; Bochicchio, Brigida; Pepe, Antonietta; Schenke-Layland, Katja; Hinderer, Svenja

2017-04-01

Actinic Keratosis' (AKs) are small skin lesions that are related to a prolonged sun-damage, which can develop into invasive squamous cell carcinoma (SCC) when left untreated. Effective, specific and well tolerable therapies to cure AKs are still of great interest. Diclofenac (DCF) is the current gold standard for the local treatment of AKs in terms of costs, effectiveness, side effects and tolerability. In this work, an electrospun polylactic acid (PLA) scaffold loaded with a synthetic DCF prodrug was developed and characterized. Specifically, the prodrug was successfully synthetized by binding DCF to a glycine residue via solid phase peptide synthesis (SPPS) and then incorporated in an electrospun PLA scaffold. The drug encapsulation was verified using multiphoton microscopy (MPM) and its scaffold release was spectrophotometrically monitored and confirmed with MPM. The scaffold was further characterized with scanning electron microscopy (SEM), tensile testing and contact angle measurements. Its biocompatibility was verified by performing a cell proliferation assay and compared to PLA scaffolds containing the same amount of DCF sodium salt (DCFONa). Finally, the effect of the electrospun scaffolds on human dermal fibroblasts (HDFs) morphology and metabolism was investigated by combining MPM with fluorescence lifetime imaging microscopy (FLIM). The obtained results suggest that the obtained scaffold could be suitable for the controlled and targeted delivery of the synthesized prodrug for the treatment of AKs. Electrospun scaffolds are of growing interest as materials for a controlled drug delivery. In this work, an electrospun polylactic acid scaffold containing a synthetically obtained Diclofenac prodrug is proposed as a novel substrate for the topical treatment of actinic keratosis. A controlled drug delivery targeted to the area of interest could enhance the efficacy of the therapy and favor the healing process. The prodrug was synthesized via solid phase

Acantholytic squamous cell carcinoma is usually associated with hair follicles, not acantholytic actinic keratosis, and is not “high risk”: Diagnosis, management, and clinical outcomes in a series of 115 cases

PubMed Central

Ogawa, Toru; Kiuru, Maija; Konia, Thomas H.; Fung, Maxwell A.

2017-01-01

Background Acantholytic squamous cell carcinoma (aSCC) is regarded as a high-risk variant of cutaneous squamous cell carcinoma (SCC). Acantholytic actinic keratosis (aAK) has been regarded as a precursor risk factor for aSCC. However, supporting evidence is limited. Objective We sought to document clinical features, histologic features, management, and outcomes in a series of aSCC cases. Methods Definitions of aSCC, aAK, and aSCC arising in association with aAK were applied to a consecutive series of aSCC cases. Clinical characteristics and outcomes were obtained from electronic medical records. Results Of 115 aSCC cases (103 patients, mean age 71.8 years), actinic keratosis was present in 23% (27/115) but only 7.8% (9/115) exhibited associated aAK. Ten cases (10/115, 9%) fulfilled strict histologic criteria for follicular SCC as previously defined, but 50 of 115 (43%) of our aSCC cases exhibited predominant involvement of follicular epithelium rather than epidermis. Clinical outcome (median follow-up, 36 months) was available in 106 of 115 (92%). One patient experienced regional extension (parotid), and 1 patient experienced a local recurrence (nose). No disease-related metastases or deaths were documented. Limitations This was a single-institution retrospective study from the United States. Conclusions The presence of acantholysis in cutaneous SCC does not specifically confer aggressive behavior, a finding that may inform clinical practice guidelines. PMID:27889291

Long-term use of a new topical formulation containing piroxicam 0.8% and sunscreen: efficacy and tolerability on actinic keratosis. A proof of concept study.

PubMed

Babino, Graziella; Diluvio, Laura; Bianchi, Luca; Orlandi, Augusto; Di Prete, Monia; Chimenti, Sergio; Milani, Massimo; Campione, Elena

2016-08-01

Cyclooxygenase (COX) 1 and 2 enzyme up-regulation is involved in the pathogenetic process of actinic keratosis (A.K.) and non-melanoma skin cancers. Diclofenac, a non-steroidal anti-inflammatory (N.S.A.I.D.) drug, is used as topical treatment of A.K. Piroxicam is a N.S.A.I.D. characterized by a high COX-1 inhibition activity. We conducted an 18 month exploratory open-label study on A.K., to assess the efficacy and tolerability of a new topical formulation of piroxicam and sunscreen in A.K. Enrolled subjects applied a galenic formulation of piroxicam 0.8%, vehiculated in a topical product containing sun filters with high (50+) and broad spectrum (UVA) actions, twice a day for 6 months. Subjects were then followed up for additional 12 months. Thirty-eight subjects with a total of 69 A.K. lesions participated in the trial. The primary outcome was the evolution of the Actinic Keratosis Erythema Scale Atrophy (A.K.E.S.A) score assessing erythema, scale, and atrophy of a target A.K. lesion. Secondary outcomes were the percentage of treated lesions with complete (100%) or partial (≥75%) clearance and the evaluation skin tolerability. A.K.E.S.A. mean (S.D.) score at baseline was 7.5 (1.2). After 6 months of treatment, A.K.E.S.A. score decreased to 0.9 (1.1), a -88% reduction versus baseline. At the end of follow-up, A.K.E.S.A. score was 0.8 (1.2). A complete response was achieved in 38 of the 69 lesions (55%, 95% C.I.: 43% to 66%) and clearance was maintained 1 year post-treatment. A partial clearance was observed in 57 of 69 treated lesions (83%, 95% C.I.: 73% to 91%). Adverse events were limited to mild local irritation. Our experience suggests that 6 month topical piroxicam 0.8% is efficacious and well tolerated in A.K. Clinical efficacy is maintained 1 year post-treatment. The main limitation of our study is that it was an open label non-controlled trial. Future controlled trials are warranted in order to compare the efficacy and tolerability of this topical

Spanish adaptation of the European guidelines for the evaluation and treatment of actinic keratosis.

PubMed

Ferrándiz, C; Fonseca-Capdevila, E; García-Diez, A; Guillén-Barona, C; Belinchón-Romero, I; Redondo-Bellón, P; Moreno-Giménez, J C; Senán, R

2014-05-01

Current trends in our setting indicate that the prevalence of actinic keratosis and similar diseases will increase in coming years and impose a greater burden on health care resources. A long list of clinical features must be taken into account when approaching the treatment of actinic keratosis. Until recently, therapeutic approaches focused solely on ablative procedures and the treatment of individual lesions and did not take into account areas of field cancerization. Now that the therapeutic arsenal has grown, standardized criteria are needed to guide the optimal choice of treatment for each patient. The elaboration of evidence-based consensus recommendations for the diagnosis and treatment of actinic keratosis generates knowledge that will help clinicians to deliver the highest level of care possible, standardizing decision-making processes and enhancing awareness among all the health professionals involved in the care pathway. Copyright © 2013 Elsevier España, S.L. and AEDV. All rights reserved.

A survey of office visits for actinic keratosis as reported by NAMCS, 1990-1999. National Ambulatory Medical Care Survey.

PubMed

Gupta, Aditya K; Cooper, Elizabeth A; Feldman, Steven R; Fleischer, Alan B

2002-08-01

Although actinic keratosis (AK) has been linked to the development of nonmelanoma skin cancer (NMSC), particularly squamous cell carcinoma (SCC), increased awareness regarding diagnosis and treatment may be an important component for reducing morbidity and even mortality from AK and NMSC. We used the National Ambulatory Medical Care Survey (NAMCS) data from 1990 to 1999 to evaluate the diagnosis and treatment of AKs among a wide variety of patients by physicians across the United States. To our knowledge, no widespread surveys of North American populations have been performed recently to determine the epidemiology of AK. AK was diagnosed in more than 47 million visits over the 10-year period surveyed and was found to occur in 14% of patients visiting dermatologists. The diagnosis of AK as determined by NAMCS does not reflect the true prevalence of AK because only patients seeking physician diagnosis were surveyed. This suggests that the actual number of patients in the United States with AK is much higher than 14%. Rates of AK diagnosis in the standard metropolitan statistical areas (SMSAs) and non-standard metropolitan statistical areas (non-SMSAs) of the West states are higher than in other states, but geographic location may not be a direct risk factor for the development of AKs. Procedures were undertaken at 70% of visits where AK was the primary diagnosis. Destruction of lesions was the most frequently performed procedure found in the survey considering only the 1993 and 1994 NAMCS data. Biopsy was the second most frequently performed procedure.

Reduced degree of irritation during a second cycle of ingenol mebutate gel 0.015% for the treatment of actinic keratosis.

PubMed

Jim On, Shelbi C; Haddican, Madelaine; Yaroshinsky, Alex; Singer, Giselle; Lebwohl, Mark

2015-01-01

Ingenol mebutate gel is a topical field treatment of actinic keratosis (AK). One of several proposed mechanisms of action for ingenol mebutate is induction of cell death in proliferating keratinocytes, suggesting a preferential action on AKs rather than healthy skin. Local skin reactions (LSRs) during 2 sequential 4-week cycles of AK treatment with ingenol mebutate gel 0.015% on the face or scalp were evaluated to test the hypothesis that reapplication of the study product would produce lower LSR scores than during the first treatment cycle. In this unblinded study, 20 participants with AKs on the face or scalp were treated with ingenol mebutate gel 0.015% once daily for 3 days in 2 sequential 4-week cycles. Composite LSR scores were evaluated during both cycles. The composite LSR score during the second cycle was found to be significantly lower than the first cycle (P=.0002). The proportion of participants who experienced LSRs in the second treatment cycle was less than the first cycle. Ingenol mebutate gel 0.015% may cumulatively reduce the burden of sun-damaged skin over 2 treatment cycles by targeting and removing transformed keratinocytes.

Influence of Information Framing on Patient Decisions to Treat Actinic Keratosis

PubMed Central

Berry, Katherine; Butt, Melissa

2017-01-01

Importance Actinic keratosis (AK) is a skin growth induced by UV light exposure that requires long-term management because a small proportion of the disease can progress to squamous cell carcinoma. The influence of how clinicians frame or present information to patients may affect decision making about AK. Objective To evaluate the differences in patients’ decisions on whether to receive treatment for AK related to information presentation or choice framing. Design, Setting, and Participants A prospective survey study was performed from June 1 to July 31, 2016, in participants who were able to read English. Participants were recruited through the Penn State Milton S. Hershey Dermatology Clinic and an online survey site. The survey was conducted through an online portal. A total of 571 individuals were recruited. Regression analysis, correlation coefficient analysis, and test-retest validation were conducted. Main Outcomes and Measures The proportions of patients choosing to receive treatment for AK. Analyses were performed to adjust for age, sex, educational level, history of skin cancer, and history of AK. Results Of the 571 recruited participants, 539 (94.4%) returned completed surveys. The mean (SD) age of respondents was 42.9 (17.8) years; 306 (56.8%) were women. The decision to receive treatment for AK varied from 57.7% (n = 311) to 92.2% (n = 497) for the 5 scenarios presented in the questions (P < .001). The question that presented AK as a “precancer” had the highest proportion of participants who preferred treatment (497 [92.2%]). Two questions that presented the risk of AK as not progressing to cancer had the lowest proportion of individuals who chose treatment (311 [57.7%] and 328 [60.9%]). Participants from the clinic and from the online portal were significantly different in age (mean [SD] age, 56.1 [17.6] vs 33.3 [10.0] years), sex (145 [63.6%] vs 161 [51.8%] were females), educational level (40 [17.5%] vs 80 [25.7%] had completed

A new, objective, quantitative scale for measuring local skin responses following topical actinic keratosis therapy with ingenol mebutate.

PubMed

Rosen, Robert; Marmur, Ellen; Anderson, Lawrence; Welburn, Peter; Katsamas, Janelle

2014-12-01

Local skin responses (LSRs) are the most common adverse effects of topical actinic keratosis (AK) therapy. There is currently no method available that allows objective characterization of LSRs. Here, the authors describe a new scale developed to quantitatively and objectively assess the six most common LSRs resulting from topical AK therapy with ingenol mebutate. The LSR grading scale was developed using a 0-4 numerical rating, with clinical descriptors and representative photographic images for each rating. Good inter-observer grading concordance was demonstrated in peer review during development of the tool. Data on the use of the scale are described from four phase III double-blind studies of ingenol mebutate (n = 1,005). LSRs peaked on days 4 (face/scalp) or 8 (trunk/extremities), with mean maximum composite LSR scores of 9.1 and 6.8, respectively, and a rapid return toward baseline by day 15 in most cases. Mean composite LSR score at day 57 was generally lower than at baseline. The LSR grading scale is an objective tool allowing practicing dermatologists to characterize and compare LSRs to existing and, potentially, future AK therapies.

Actinic Keratosis and Non-Invasive Diagnostic Techniques: An Update

PubMed Central

Casari, Alice; Chester, Johanna; Pellacani, Giovanni

2018-01-01

Actinic keratosis represents the earliest manifestation of non-melanoma skin cancer. Because of their risk of progression to invasive squamous cell carcinoma, an earlier diagnosis and treatment are mandatory. Their diagnosis sometimes could represent a challenge even for expert dermatologists. Dermoscopy, confocal laser microscopy and optical coherence tomography could help clinicians in diagnosis. PMID:29316678

Factors influencing response to ingenol mebutate therapy for actinic keratosis of face and scalp

PubMed Central

Skroza, Nevena; Proietti, Ilaria; Bernardini, Nicoletta; Balduzzi, Veronica; Mambrin, Alessandra; Marchesiello, Anna; Tolino, Ersilia; Zuber, Sara; La Torre, Giuseppe; Potenza, Concetta

2017-01-01

AIM To determine factors independently influencing response to ingenol mebutate therapy and assess efficacy on clinical setting of non-hypertrophic non-hyperkeratotic actinic keratosis (AK). METHODS Consecutive patients affected by non-hypertrophic non-hyperkeratotic AKs of the face or scalp were enrolled to receive ingenol mebutate 0.015% gel on a selected skin area of 25 cm2 for 3 consecutive days. Local skin reactions were calculated at each follow up visit using a validated composite score. Efficacy was evaluated by the comparison of clinical and dermoscopic pictures before the treatment and at day 57, and classified as complete, partial and poor response. RESULTS A number of 130 patients were enrolled, of which 101 (77.7%) were treated on the face, while 29 (22.3%) on the scalp. The great majority of our study population (n = 119, 91.5%) reached at least a 75% clearance of AKs and, in particular, 58 patients (44.6%) achieved a complete response while 61 (46.9%) a partial one. Logistic backward multivariate analysis showed that facial localization, level of local skin reaction (LSR) at day 2, the highest LSR values and level of crusts at day 8 were factors independently associated with the achievement of a complete response. CONCLUSION Ingenol mebutate 0.015% gel, when properly applied, is more effective on the face than on the scalp and efficacy is directly associated to LSR score. PMID:29067277

Cost-effectiveness of Ingenol Mebutate Gel for the Treatment of Actinic Keratosis in Greece.

PubMed

Athanasakis, Kostas; Boubouchairopoulou, Nadia; Tarantilis, Filippos; Tsiantou, Vasiliki; Kontodimas, Stathis; Kyriopoulos, John

2017-05-01

The present study aimed to perform a cost-effectiveness analysis of ingenol mebutate (IM) versus other topical alternatives for the treatment of actinic keratosis (AK). The analysis used a decision tree to calculate the clinical effects and costs of AK first-line treatments, IM (2-3 days), diclofenac 3% (for 8 or 12 weeks), imiquimod 5% (for 4 or 8 weeks), during a 24-month horizon, using discrete intervals of 6 months. A hypothetical cohort of immunocompetent adult patients with clinically confirmed AK on the face and scalp or trunk and extremities was considered. Clinical data on the relative efficacy were obtained from a network meta-analysis. Inputs concerning resource use derived from an expert panel. All costs were calculated from a Greek third-party payer perspective. IM 0.015% and 0.05% were both cost-effective compared with diclofenac and below a willingness-to-pay threshold of €30,000 per quality-adjusted life-year (QALY) (€199 and €167 per QALY, respectively). Comparing IM on the face and scalp AK lesions for 3 days versus imiquimod for 4 weeks resulted in an incremental cost-effectiveness ratio of €10,868 per QALY. IM was dominant during the 8-week imiquimod period. IM use on the trunk and extremities compared with diclofenac (8 or 12 weeks) led to incremental cost-effectiveness ratios estimated at €1584 and €1316 per QALY accordingly. Results remained robust to deterministic and probabilistic sensitivity analyses. From a social insurance perspective in Greece, IM 0.015% and IM 0.05% could be the most cost-effective first-line topical field treatment options in all cases for AK treatment. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

In vivo Confocal Laser Microscopy for monitoring of actinic keratosis treatment: a comparison with histopathologic assessment after treatment with topical 5% 5-fluorouracil.

PubMed

Ishioka, P; Maia, M; Rodrigues, S B; Lellis, R F; Hirata, S H

2017-11-24

Histological examination is the gold standard for actinic keratosis diagnosis; however, it is not always a feasible approach. Reflectance confocal microscopy (RCM) is a non-invasive technique that may be an alternative for monitoring actinic keratoses treatment response. Topical 5-fluorouracil is indicated for actinic keratosis multiple lesions and for field cancerization treatment. To assess the RCM accuracy, sensibility and specificity for actinic keratosis, considering as a gold standard the histopathological examination; as well as to evaluate the efficacy of 5% 5-fluorouracil treatment. This is a prospective study in actinic keratosis patients between August 2014 and November 2015. RCM analyses were performed in one randomly selected actinic keratosis lesion of the upper limbs by two independent observers before and after 5% 5-fluorouracil treatment. At the end of treatment and with clinical bleaching of treated lesions, histological examination was performed by two pathologists. A total of 50 lesions were enroled, and 40 lesions presented complete clinical bleaching after treatment and were included in the final analysis. Accuracy, sensibility and specificity means among observers were 83.8%, 84.6% and 83.3%, respectively. After 5-fluorouracil treatment, actinic keratosis was diagnosed in 45.0% (observer 1) and 32.5% (observer 2) of subjects according to RCM and in 32.5% of subjects according to histological examination. Considering RCM observers diagnosis, the concordance was substantial (k 0.637, P < 0.001). 5-fluorouracil led to a reduction in 55.0%-67.5% of actinic keratoses according to RCM analysis. This study allows to validate RCM as a non-invasive method capable of monitoring actinic keratosis therapeutic response to 5-fluorouracil, presenting efficacy comparable to histological examination. Additionally, the results suggest that 5-fluorouracil may be a satisfactory option for therapeutic control of this condition. © 2017 European Academy of

Increased number of mast cells in the dermis in actinic keratosis lesions effectively treated with imiquimod.

PubMed

Oyama, Satomi; Funasaka, Yoko; Tsuchiya, Shin-Ichi; Kawana, Seiji; Saeki, Hidehisa

2017-08-01

Actinic keratosis (AK) is a cutaneous cancer in situ which develops as a result of excessive exposure to ultraviolet (UV). Toll-like receptor (TLR)7 agonist imiquimod is a topical immune response modifier and is effective for the treatment of non-melanoma skin cancers. Recently, the diagnostic role of the dermatoscope has been reported in the course of treatment of AK. In addition, mast cells are now considered to contribute to both the innate and adaptive immune systems in topical imiquimod therapy. We assessed the effect of imiquimod treatment by dermatoscopic and immunohistochemical findings in 14 patients with a total of 21 AK lesions. With the dermatoscope, though the mean erythema score was not significantly different between the cured lesions and the unresponsive lesions, the erythema/red pseudo-network ("strawberry") pattern was decreased significantly in the cured lesions. By immunohistochemistry, the number of Ki-67-positive proliferative cells in the epidermis was decreased and that of CD117-positive mast cells in the dermis was increased in the responding lesions. To the best of our knowledge, this is the first study demonstrating that the number of mast cells in the dermis was increased in AK lesions effectively treated with imiquimod. Our present result suggests that mast cells may contribute an antitumor effect in human skin treated with topical imiquimod. © 2017 Japanese Dermatological Association.

Dermoscopic clues to differentiate facial lentigo maligna from pigmented actinic keratosis.

PubMed

Lallas, A; Tschandl, P; Kyrgidis, A; Stolz, W; Rabinovitz, H; Cameron, A; Gourhant, J Y; Giacomel, J; Kittler, H; Muir, J; Argenziano, G; Hofmann-Wellenhof, R; Zalaudek, I

2016-05-01

Dermoscopy is limited in differentiating accurately between pigmented lentigo maligna (LM) and pigmented actinic keratosis (PAK). This might be related to the fact that most studies have focused on pigmented criteria only, without considering additional recognizable features. To investigate the diagnostic accuracy of established dermoscopic criteria for pigmented LM and PAK, but including in the evaluation features previously associated with nonpigmented facial actinic keratosis. Retrospectively enrolled cases of histopathologically diagnosed LM, PAK and solar lentigo/early seborrhoeic keratosis (SL/SK) were dermoscopically evaluated for the presence of predefined criteria. Univariate and multivariate regression analyses were performed and receiver operating characteristic curves were used. The study sample consisted of 70 LMs, 56 PAKs and 18 SL/SKs. In a multivariate analysis, the most potent predictors of LM were grey rhomboids (sixfold increased probability of LM), nonevident follicles (fourfold) and intense pigmentation (twofold). In contrast, white circles, scales and red colour were significantly correlated with PAK, posing a 14-fold, eightfold and fourfold probability for PAK, respectively. The absence of evident follicles also represented a frequent LM criterion, characterizing 71% of LMs. White and evident follicles, scales and red colour represent significant diagnostic clues for PAK. Conversely, intense pigmentation and grey rhomboidal lines appear highly suggestive of LM. © 2015 British Association of Dermatologists.

Adaptation and validation of the Spanish version of the Actinic Keratosis Quality of Life questionnaire.

PubMed

Longo Imedio, Isabel; Serra-Guillén, Carlos

2016-01-01

While there are questionnaires for evaluating the effects of skin cancer on patient quality of life, there are no specific questionnaires available in Spanish for evaluating quality of life in patients with actinic keratosis. The aim of this study was to translate and culturally adapt the Actinic Keratosis Quality of Life (AKQoL) questionnaire into Spanish. The original questionnaire was translated into Spanish following the guidelines for the cross-cultural adaptation of self-report measures. Several measures of general reliability and validity were calculated, including Cronbach α for internal consistency and the Spearman rank-order correlation coefficient and a Bland-Altman plot for test-retest reliability. To test concurrent validity, we used the Pearson correlation coefficient to measure the correlation between AKQoL and Skindex-29 scores. The final version of the questionnaire was administered to 621 patients with actinic keratosis, who scored a mean (SD) of 5.25 (4.73) points (total possible score, 0-25). The Cronbach α reliability coefficient analysis was 0.84. The correlation between the mean (SD) score on the Skindex-29 (1.87 [4.07]) and on the AKQoL (1.97 [2.98] was 0.344 (P=.002, Spearman's rho), with a proportion of shared variance of 11.8%. The translation, cross-cultural adaptation, and validation of the original AKQoL produced a reliable, easily understandable questionnaire for evaluating the impact of actinic keratosis on the quality of life of patients in our setting. Copyright © 2016 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

Randomized, Controlled Trial of Fractional Carbon Dioxide Laser Resurfacing Followed by Ultrashort Incubation Aminolevulinic Acid Blue Light Photodynamic Therapy for Actinic Keratosis.

PubMed

Alexiades, Macrene

2017-08-01

Aminolevulinic acid (ALA) photodynamic therapy (PDT) is an established treatment option for actinic keratosis (AK), and recently fractional carbon dioxide (CO2) laser was shown to improve outcomes; but studies of short incubation photosensitizer are lacking. Assess the efficacy of short incubation ALA followed by blue light PDT with and without previous fractional CO2 treatment for the treatment of AK. Randomized, paired split-design, controlled trial of fractional CO2 followed by ultrashort 15-minute versus 30-minute incubation ALA and blue light PDT for the treatment of AK on the face. The complete clearance rates (CRs) at 8 weeks after ALA PDT with and without FxCO2 at 30- and 15-minute ALA incubation times were 89.78% (+FxCO2) versus 71.20% CR (-FxCO2) at 30', and 86.38% (+FxCO2) versus 69.23% (-FxCO2) at 15' ALA incubation. All lesion improvements were statistically significant. This randomized, comparative paired group controlled clinical study demonstrates that ultrashort 15- and 30-minute incubation ALA PDTs are of limited efficacy for the treatment of AK. Pretreatment with fractional ablative resurfacing yields statistically significant greater AK clearance with ALA-PDT at ultrashort ALA incubations followed by blue light.

Diagnostic accuracy of optical coherence tomography in actinic keratosis and basal cell carcinoma.

PubMed

Olsen, J; Themstrup, L; De Carvalho, N; Mogensen, M; Pellacani, G; Jemec, G B E

2016-12-01

Early diagnosis of non-melanoma skin cancer (NMSC) is potentially possible using optical coherence tomography (OCT) which provides non-invasive, real-time images of skin with micrometre resolution and an imaging depth of up to 2mm. OCT technology for skin imaging has undergone significant developments, improving image quality substantially. The diagnostic accuracy of any method is influenced by continuous technological development making it necessary to regularly re-evaluate methods. The objective of this study is to estimate the diagnostic accuracy of OCT in basal cell carcinomas (BCC) and actinic keratosis (AK) as well as differentiating these lesions from normal skin. A study set consisting of 142 OCT images meeting selection criterea for image quality and diagnosis of AK, BCC and normal skin was presented uniformly to two groups of blinded observers: 5 dermatologists experienced in OCT-image interpretation and 5 dermatologists with no experience in OCT. During the presentation of the study set the observers filled out a standardized questionnaire regarding the OCT diagnosis. Images were captured using a commercially available OCT machine (Vivosight ® , Michelson Diagnostics, UK). Skilled OCT observers were able to diagnose BCC lesions with a sensitivity of 86% to 95% and a specificity of 81% to 98%. Skilled observers with at least one year of OCT-experience showed an overall higher diagnostic accuracy compared to inexperienced observers. The study shows an improved diagnostic accuracy of OCT in differentiating AK and BCC from healthy skin using state-of-the-art technology compared to earlier OCT technology, especially concerning BCC diagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Using photodynamic therapy to estimate effectiveness of innovative combined diclofenac and tazaroten therapy of disseminated actinic keratosis.

PubMed

Osiecka, Beata J; Jurczyszyn, Kamil; Nockowski, Piotr; Lipinski, Artur; Sieja, Agnieszka; Ziółkowski, Piotr

2015-01-01

Early diagnosis and therapy of precancerous lesions and malignant tumors belong to the most challenging tasks in modern medicine. Photodynamic diagnosis can help diagnose both precancerous lesions and early carcinoma. Actinic keratosis (AK) is the most common precancerous lesion of the skin. The available data show a high effectiveness of diclofenac in treating multifocal AK. We report a case of a 52-year-old woman who complained of multiple disseminated AK lesions predominantly on the lower limbs and trunk with a significant exacerbation within the last 6 months. Due to the spreading of disease and a high number of AK foci, as well as technical problems with visiting the hospital (PDT Laboratory), photodynamic therapy was not applied. The patient was treated for 2 months with a combination of local administration of 3% diclofenac and 0.1% tazaroten and 3% diclofenac only as a half side (left-right) comparison. The effects of therapy were later clinically evaluated and verified by means of photodynamic diagnosis (PDD) directly after therapy and at a follow-up examination 3 months later. The evaluation of treatment was blinded. Treatment with diclofenac only on the right side of the body resulted in clearing of 55% of all treated lesions, which increased to 60% three months after finishing therapy. On the left side of the body, where combined therapy (diclofenac 2 times daily on uneven dates and diclofenac once a day + tazaroten once a day on even dates) was used, 77.5% pathologic lesions disappeared, but this did not increase at follow up. The treatment of multifocal, disseminated AK is a difficult task and also burdensome for the patient due to side effects like scarring or burning and itching which occur during most therapies. Combined therapy with diclofenac and tazaroten supported by PDD may improve the effects of routine treatment of AK.

Cytological diagnosis of basal cell carcinoma and actinic keratosis, using Papanicolaou and May-Grünwald-Giemsa stained cutaneous tissue smear.

PubMed

Christensen, E; Bofin, A; Gudmundsdóttir, I; Skogvoll, E

2008-10-01

Cytology may become the diagnostic method of choice with the advent of new non-invasive treatments for non-melanoma skin cancer, as the sampling technique for cytology entails little tissue disfiguration. The aim of this study was to compare and evaluate the diagnostic performance of scrape cytology using two different cytological staining techniques, and to evaluate additional touch imprint cytology, with that of histopathology of basal cell carcinoma (BCC) and actinic keratosis (AK). We investigated 50 BCC and 28 AK histologically verified lesions, from 41 and 25 patients, respectively. Two separate skin scrape samples and one touch imprint sample were taken from each lesion. The smears were stained with Papanicolaou (Pap) or May-Grünwald-Giemsa (MGG) stains. All cytological specimens were examined in random order by pathologists without knowledge of the histology. Cytodiagnostic results were compared with the histopathological report. Scrape cytodiagnosis agreed with histopathology in 48 (Pap) and 47 (MGG) of the 50 BCC cases, and in 26 of 28 (Pap) and 21 of 26 (MGG) AK cases, yielding sensitivities of 96%, 94%, 93% and 81%, respectively. No significant difference in sensitivity between the two staining methods was found but a trend towards higher Pap sensitivity for AK was noted (P = 0.10). Touch imprint cytology confirmed histopathology in 38 of the 77 cases of BCC and AK. Cytological diagnosis with either Pap or MGG stain for BCC and AK is reliable, and differentiates well between BCC and AK. Imprint cytology proved to be non-diagnostic in half of the examined cases.

Colonisation of basal cell carcinoma and actinic keratosis by malignant melanoma in situ in a patient with xeroderma pigmentosum variant

PubMed Central

Smith, Louise J.; Husain, Ehab A.

2012-01-01

Although malignant melanoma (MM) and both basal cell carcinoma (BCC) and actinic keratosis (AK) are sun-induced lesions, the coexistence of these entities at the same anatomical site (collision tumour) is exceedingly rare. We report the case of a 54-year-old woman with a known history of xeroderma pigmentosum variant (XPV) who presented with 2 separate skin lesions over the middle and upper right forearm, respectively. The clinical impression was that of BCCs or squamous cell lesions. On histological examination, both specimens showed features of melanoma in situ (MIS). In the first lesion, MIS merged with and colonised a superficial and focally invasive BCC. In the second lesion, MIS merged with an AK. No separate invasive nests of malignant melanoma were seen in either specimen. The atypical melanocytes were highlighted by Melan-A and HMB-45 immunostaining, whereas the epithelial cells in both the BCC and AK stained with the pancytokeratin MNF-116. The patient had a previous history of multiple MMs and non-melanomatous skin cancers and finally developed widespread metastatic malignant melanoma, which proved fatal. The rare and interesting phenomenon of collision tumours may pose diagnostic difficulties. To our knowledge, this is the first reported simultaneous presentation of cytologically malignant collision tumours in a patient with XPV. PMID:24765446

Evaluation of the therapeutic results of actinic keratosis treated with topical 5% fluorouracil by reflectance confocal laser microscopy: preliminary study*

PubMed Central

Ishioka, Priscila; Maia, Marcus; Rodrigues, Sarita Bartholomei; Marta, Alessandra Cristina; Hirata, Sérgio Henrique

2015-01-01

Topical treatment for actinic keratosis with 5% fluorouracil has a recurrence rate of 54% in 12 months of follow-up. This study analyzed thirteen actinic keratoses on the upper limbs through confocal microscopy, at the time of clinical diagnosis and after 4 weeks of treatment with fluorouracil. After the treatment was established and evidence of clinical cure was achieved, in two of the nine actinic keratoses, confocal microscopy enabled visualization of focal areas of atypical honeycomb pattern in the epidermis indicating therapeutic failure. Preliminary data suggest the use of confocal microscopy as a tool for diagnosis and therapeutic control of actinic keratosis. PMID:26131881

A 12-Day Course of Imiquimod 5% for the Treatment of Actinic Keratosis: Effectiveness and Local Reactions.

PubMed

Serra-Guillén, C; Nagore, E; Llombart, B; Sanmartín, O; Requena, C; Calomarde, L; Guillén, C

2018-04-01

Imiquimod is an excellent option for patients with actinic keratosis, although its use may be limited by the long course of treatment required (4 weeks) and the likelihood of local skin reactions. The objectives of the present study were to demonstrate the effectiveness of a 12-day course of imiquimod 5% for the treatment of actinic keratosis and to examine the association between treatment effectiveness and severity of local reactions. We included patients with at least 8 actinic keratoses treated with imiquimod 5% cream for 12 consecutive days. Local reactions were classified as mild, moderate, or severe. The statistical analysis of the association between local reactions and clinical response was based on the Pearson χ 2 test and the Spearman rank correlation test. Sixty-five patients completed the study. Complete response was recorded in 52.3% and partial response in 75.4%. We found a statistically significant association between severity of the local reaction and response to treatment in both the Pearson χ 2 test and the Spearman rank correlation test. A 12-day course of imiquimod 5% proved effective for the treatment of actinic keratosis. Severity of local reactions during treatment was correlated with clinical response. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Topical photodynamic therapy with methylaminolevulinate for the treatment of actinic keratosis and reduction of photodamage in organ transplant recipients: a case-series of 16 patients.

PubMed

Hasson, Ariel; Navarrete-Dechent, Cristián; Nicklas, Claudia; de la Cruz, Claudia

2012-01-01

Organ transplant recipients (OTR) are at high risk of developing cutaneous neoplasms. Topical photodynamic therapy (PDT) has been used for the treatment of actinic keratosis (AK) in OTR. The objective was to evaluate the efficacy of PDT with methylaminolevulinate (MAL) in the treatment of facial AK in OTR. As a secondary objective, we wanted to evaluate the usefulness of topical PDT in the reduction of photodamage in OTR. A prospective, single center, single arm study was made. 16 OTR were included. Topical PDT was applied for 1 or 2 cycles depending on the patient's characteristics. An evaluation of AK was made at visits pre-treatment, at 12 weeks and at 24 weeks. Photodamage was measured with multispectral image technique (SkinCare). A complete response rate of 100% was achieved for AK in all patients; it persisted without change at 12 and 24 weeks of follow-up. 62.5% of patients improved their photodamage as measured by SkinCare®, but this result was not statistically significant (P = 0.12). All patients had high level of satisfaction at the end of the therapy. MAL-PDT is an effective therapy for the treatment of AK in OTRs. It can reduce photodamage in this group of patients, but these results were not statistically significant.

Comparative study of trichloroacetic acid vs. photodynamic therapy with topical 5-aminolevulinic acid for actinic keratosis of the scalp.

PubMed

Di Nuzzo, Sergio; Cortelazzi, Chiara; Boccaletti, Valeria; Zucchi, Alfredo; Conti, Maria Luisa; Montanari, Paola; Feliciani, Claudio; Fabrizi, Giuseppe; Pagliarello, Calogero

2015-09-01

Photodynamic therapy with 5-methyl-aminolevulinate and photodynamic therapy with trichloroacetic acid 50% are the two techniques utilized in the management of actinic keratosis. This study was planned to compare the efficacy, adverse effects, recurrence and cosmetic outcome of these option therapies in patients with multiple actinic keratosis of the scalp. Thirteen patients with multiple actinic keratosis were treated with one of the two treatments on half of the scalp at baseline, while the other treatment was performed on the other half 15 days apart, randomly. Efficacy, adverse effects, cosmetic outcome and recurrence were recorded at follow-up visit at 1, 3, 6 and 12 months. Photodynamic therapy with 5 methyl-aminolevulinate was more effective than trichloroacetic acid although less tolerated by patients as it was more painful. Early adverse effects were almost the same even if trichloroacetic acid leads also to crust formation and to a worse cosmetic outcome characterized by hypopigmentation. Recurrence was lower in the area treated with photodynamic therapy. Trichloroacetic acid 50% is less effective than photodynamic therapy with 5 methyl-aminolevulinate in the treatment of multiple actinic keratosis of the scalp although better tolerated by patients. As this technique is less painful and less expensive than photodynamic therapy, we hypothesize and suggest that more sequential treatments could lead to better results. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PDT and emerging therapies for Actinic Keratosis-A resource letter.

PubMed

Filho, José D Vollet; Andrade, Cintia T; Buzza, Hilde H; Blanco, Kate; Carbinatto, Fernanda; Bagnato, Vanderlei S; Allison, Ron R

2017-03-01

Aktinic Keratosis is common and if left untreated may develop into life threatening squamous cell carcinoma. Therefore early intervention is the standard of care. While many treatments are available PDT continues to move to the for - front for this indication (Brito et al., 2016 [31]). Topical PS is commercially available that are able to reliably ablate these lesions. Innovative protocols including sunlight, large volume LED arrays and maneuvers to improve treatment parameters and cosmesis continue to make this a worldwide treatment of choice for AK. Copyright © 2016 Elsevier B.V. All rights reserved.

Cost-effectiveness analysis of 5-fluorouracil 0.5%/salicylic acid 10% in the treatment of actinic keratosis in Spain.

PubMed

Nieves, Diana; Puig-Peiró, Ruth; Ferrándiz, Carlos; Plazas, Maria Josep; Brosa, Max

2015-06-01

The aim of this study is to conduct a cost-effectiveness analysis of 5-fluorouracil 0.5%/salicylic acid 10% (5-FU/SA) in the treatment of isolated hyperkeratotic actinic keratosis lesions in Spain. An analytical decision-making model was constructed to compare whether 5-FU/SA was a cost-effective option compared with cryotherapy from the perspective of the Spanish National Health System with a time horizon of 6 months. Costs were expressed in 2014 euros. The cost of patients with hyperkeratotic actinic keratosis treated with 5-FU/SA or cryotherapy was €266 and €285, respectively. 5-FU/SA was associated with higher rates of treatment success and, consequently, more quality-adjusted life years, than cryotherapy. Therefore, 5-FU/SA was the dominant treatment, as it was associated with a lower treatment cost and greater effectiveness than cryotherapy. Economically, 5-FU/SA was a dominant option compared with cryotherapy in the treatment of isolated hyperkeratotic actinic keratosis lesions in Spain.

Photodynamic therapy effective for the treatment of actinic keratosis and basal cell carcinoma in bullous pemphigoid patients.

PubMed

Canavan, Theresa N; de la Feld, Salma Faghri; Huang, Conway; Sami, Naveed

2017-06-01

Treating skin cancers and extensive actinic keratosis in patients with bullous pemphigoid (BP) can be challenging. Treatment options pose unique risks in these patients as surgical wounds can have delayed wound healing and photodynamic therapy (PDT) may exacerbate their blistering disease. We report the successful use of PDT to treat actinic keratosis and skin cancers in two patients with BP, both of whom had excellent response to PDT and tolerated treatment without any bullous disease flares. Carefully selected patients with skin cancers and stable, well controlled BP can be safely considered for treatment using PDT. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of T-lymphocyte subpopulations in actinic keratosis, in situ and invasive squamous cell carcinoma of the skin.

PubMed

Stravodimou, Aristea; Tzelepi, Vassiliki; Papadaki, Helen; Mouzaki, Athanasia; Georgiou, Sophia; Melachrinou, Maria; Kourea, Eleni P

2018-05-01

Tumor infiltrating lymphocytes (TILs) represent important regulators of carcinogenesis. Cutaneous invasive squamous cell carcinoma (inSCC) develops through precursor lesions, namely in situ squamous cell carcinoma (isSCC) and actinic keratosis (AK), representing a natural model of carcinogenesis. The study evaluates TIL subpopulations in inSCC and its precursors by comparing 2 semiquantitative scoring systems, and assesses the presence of regulatory T-cells (Tregs) in these lesions. Paraffin sections from 33 cases of AK, 19 isSCCs and 34 inSCCs with adjacent precursor lesions or normal skin (NS) were immunostained for CD3, CD4, CD8 and Foxp3. TIL subgroups were evaluated by the semiquantitative Klintrup-Mäkinen (K-M) score, and by a more detailed modification of this system. Treg counts were assessed by image analysis quantification. An increase of all TIL subpolulations from precursor lesions toward inSCC was shown by both scoring systems. Treg counts progressively increased from NS to AK and isSCC, but decreased in inSCC. Tregs were more numerous in pT2 and around indolent inSCCs compared to T1 and aggressive subtypes. T-cells and cytotoxic T-cells progressively increase in cutaneous squamous cell carcinogenesis, while Treg counts diminish in inSCC. The K-M score is an appropriate, easily applicable TIL scoring system in cutaneous inSCC. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluation of Resource Utilization and Treatment Patterns in Patients with Actinic Keratosis in the United States.

PubMed

Asche, Carl V; Zografos, Panagiotis; Norlin, Jenny M; Urbanek, Bill; Mamay, Carl; Makin, Charles; Erntoft, Sandra; Chen, Chi-Chang; Hines, Dionne M; Mark Siegel, Daniel

2016-01-01

To compare health care resource utilization and treatment patterns between patients with actinic keratosis (AK) treated with ingenol mebutate gel (IngMeb) and those treated with other field-directed AK therapies. A retrospective, propensity-score-matched, cohort study compared refill/repeat and adding-on/switching patterns and outpatient visits and prescriptions (health care resource utilization) over 6 months in patients receiving IngMeb versus those receiving imiquimod, 5-fluorouracil, diclofenac sodium, and methyl aminolevulinate or aminolevulinic acid photodynamic therapy (MAL/ALA-PDT). The final sample analyzed included four matched treatment cohort pairs (IngMeb and comparator; n = 790-971 per treatment arm). Refill rates were similar except for imiquimod (15% vs. 9% for imiquimod and IngMeb, respectively; P < 0.05). MAL/ALA-PDT treatment repetition rates were higher than IngMeb refill rates (20% vs. 10%; P < 0.05). Topical agent add-on/switch rates were comparable. PDT had higher switch rates than did IngMeb (5% vs. 2%; P < 0.05). The IngMeb cohort had a significantly lower proportion of patients with at least one AK-related outpatient visit during the 6-month follow-up than did any other cohort: versus imiquimod (50% vs. 66%; P < 0.0001), versus 5-fluorouracil (50% vs. 69%; P < 0.0001), versus diclofenac sodium (51% vs. 56%; P = 0.034), and versus MAL/ALA-PDT (50% vs. 100%; P < 0.0001). There were significantly fewer AK-related prescriptions among patients receiving IngMeb than among patients in other cohorts. Results based on the first 6 months after treatment initiation suggested that most field-directed AK therapies had clinically comparable treatment patterns except imiquimod, which was associated with higher refill rates, and PDT, which was associated with significantly more frequent treatment sessions and higher switching rates. IngMeb was also associated with significantly fewer outpatient visits than were other field-directed therapies. Copyright �

Actinic keratosis modelling in mice: A translational study

PubMed Central

Vandenberghe, Isabelle; Cartron, Valérie; Cèbe, Patrick; Blanchet, Jean-Christophe; Sibaud, Vincent; Guilbaud, Nicolas; Audoly, Laurent; Lamant, Laurence; Kruczynski, Anna

2017-01-01

Background Actinic keratoses (AK) are pre-malignant cutaneous lesions caused by prolonged exposure to ultraviolet radiation. As AKs lesions are generally accepted to be the initial lesions in a disease continuum that progresses to squamous cell carcinoma (SCC), AK lesions have to be treated. They are also the second most common reason for visits to the dermatologist. Several treatments are available but their efficacy still needs to be improved. The UV-B-induced KA lesion mouse model is used in preclinical studies to assess the efficacy of novel molecules, even though it is often more representative of advanced AK or SCC. Objectives Here we report on a translational study, comparing the various stages of AK development in humans and in the UV-B irradiated mouse model, as well as the optimization of photograph acquisition of AK lesions on mouse skin. Methods Human and mouse skin lesions were analysed by histology and immunohistochemistry. Mouse lesions were also assessed using a digital dermatoscope. Results An histological and phenotypic analysis, including p53, Ki67 and CD3 expression detection, performed on human and mouse AK lesions, shows that overall AK modelling in mice is relevant in the clinical situation. Some differences are observed, such as disorganization of keratinocytes of the basal layer and a number of atypical nuclei which are more numerous in human AK, whereas much more pronounced acanthosis is observed in skin lesion in mice. Thanks to this translational study, we are able to select appropriate experimental conditions for establishing either early or advanced stage AK or an SCC model. Furthermore, we optimized photograph acquisition of AK lesions on mouse skin by using a digital dermatoscope which is also used in clinics and allows reproducible photograph acquisition for further reliable assessment of mouse lesions. Use of this camera is illustrated through a pharmacological study assessing the activity of CARAC®. Conclusion These data

[Actinic keratosis, Bowen's disease, keratoacanthoma and squamous cell carcinoma of the skin].

PubMed

Majores, M; Bierhoff, E

2015-02-01

Actinic (solar) keratosis is an intraepidermal squamous neoplasm of sun-damaged skin and by far the most frequent neoplastic skin lesion. A subdivison into three grades has been proposed with increasing acceptance not least because of the therapeutic consequences. The transition to invasive squamous cell carcinoma is reported in 5-10 % and with immunosuppression in 30 % of patients.Bowen's disease is a variant of squamous cell carcinoma in situ of the skin and the mucocutaneous junction. The differentiation from bowenoid papulosis as a lesion associated with human papillomavirus (HPV), actinic (solar) keratosis grade III, intraepidermal poroid lesions and in cases of clonal type from clonal seborrhoic keratosis and Paget's disease is very important.Keratoacanthoma is currently uniformly interpreted as a variant of highly differentiated squamous cell carcinoma of the skin with clinical and histomorphological characteristics. Clinically keratoacanthoma erupts rapidly and is capable of resolving spontaneously. Histologically, there is a characteristic growth pattern and various stages of regression. The final histomorphological diagnosis needs the entire specimen.Squamous cell carcinoma of the skin is the second most common type of skin cancer following basal cell carcinoma. With respect to reccurrencies and risk of metastases the subtyping of cutaneous squamous cell carcinoma is very important. The classification system of the Union Internationale Contra le Cancer (UICC) is based solely on the anatomical spread and the classification system of the American Joint Committee on Cancer (AJCC) also considers so-called high-risk features in the staging between stages I and II.

Quality of life and side effects in patients with actinic keratosis treated with ingenol mebutate: a pilot study.

PubMed

Jubert-Esteve, E; Del Pozo-Hernando, L J; Izquierdo-Herce, N; Bauzá-Alonso, A; Martín-Santiago, A; Jones-Caballero, M

2015-10-01

Actinic keratosis (AK) lesions are in situ squamous cell carcinoma. These lesions have a low risk of progressing to invasive disease but significant impact on patients' quality of life (QoL). The aim of this study was to assess QoL and side effects in patients with AK receiving treatment with ingenol mebutate. This was a prospective, non-randomized pilot study carried out in Spain. The target population was adults with a clinical diagnosis of AK affecting any part of the body. Outcomes were assessed on the basis of a QoL questionnaire (Skindex-29), local skin response, the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4), and clinical response. A total of 19 patients were studied. Most of the participants were men (89.5%) and mean age was 76.2 years. After treatment with ingenol mebutate, significant improvement was observed in the Skindex-29 subscales relating to symptom severity (P=.041), the patients' emotional state (P=.026), and in the overall score (P=.014). Erythema, crusting, and flaking or scaling were the local skin responses with highest median score (2.0 in all 3 cases). Imiquimod 5% and ingenol mebutate achieved higher median scores for effectiveness and global satisfaction than any other previous treatments (as measured by TSQM 1.4). In the patients' assessment of convenience, ingenol mebutate had a higher median score than previous treatments. Over half of the patients (52.6%) had an improvement of at least 75% at month 3. QoL in patients with AK improves after treatment with ingenol mebutate. The presence of side effects did not affect QoL or patient satisfaction with treatment. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

Prevalence of actinic keratosis among dermatology outpatients in Spain.

PubMed

Ferrándiz, C; Plazas, M J; Sabaté, M; Palomino, R

2016-10-01

Actinic keratoses (AKs) are common skin lesions associated with an increased risk of developing squamous cell carcinoma. Few studies in Europe have focused on AK prevalence. To determine the point prevalence of AKs in a dermatology outpatient population in Spain, to describe the clinical characteristics of these lesions and to characterise the profile of AK patients. Observational, cross-sectional, multicentre study conducted in 19 hospitals (dermatology outpatient services) around Spain. A total of 204 consecutive patients per hospital who were ≥45 years old were screened for the presence of AKs. 3877 patients were assessed and the overall AKs prevalence was 28.6%. Prevalence was significantly higher in men than women (38.4% vs. 20.8%, p<0.0001) and increased with age for both sexes (45.2% in 71-80 years). Scalp and ear lesion locations were significantly more frequent in men (51.9% vs. 2.7% and 16.9% vs. 2.4%, respectively, p<0.0001 both cases) and the cheek, nose and neckline in women (46.3% vs. 34.0% [p<0.0001], 43.0% vs. 24.8% [p<0.0001] and 5.3% vs. 1.8% [p=0.002]). Men showed a significantly higher frequency of ≥2 affected areas than women (42.7% vs. 20.3%, p<0.0001). Among patients with AK lesions, only 65% confirmed that they were the reason for the visit to the clinic. Approximately a quarter of the dermatology outpatient population in Spain aged ≥45 years old have AKs, with the prevalence rate being highest in men and in older age groups. AK is underdiagnosed and a proactive strategy is needed for the diagnosis and early treatment of these lesions. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials.

PubMed

Lebwohl, Mark; Dinehart, Scott; Whiting, David; Lee, Peter K; Tawfik, Naji; Jorizzo, Joseph; Lee, James H; Fox, Terry L

2004-05-01

The immune system plays a critical role in the development and pathogenesis of actinic keratosis (AK). Imiquimod has been shown to stimulate the cutaneous immune response and be effective for the treatment of nonmelanoma skin cancers. Two phase III, randomized, double-blind, vehicle-controlled studies evaluated the efficacy of imiquimod 5% cream compared with vehicle in the treatment of AK lesions on the face and balding scalp. A total of 436 participants at 24 centers in the United States and Canada were randomized to either imiquimod 5% or vehicle cream. Study cream was applied one time per day, 2 days per week for 16 weeks. Clearance of AK lesions was clinically assessed at an 8-week posttreatment visit. The complete clearance rate was 45.1% for the imiquimod group and 3.2% for the vehicle group. The difference in complete clearance rates (imiquimod minus vehicle) was 41.9% with a 95% confidence interval of 34.9% to 49%. The partial (> or =75%) clearance rate was 59.1% for the imiquimod group and 11.8% for the vehicle group. The difference in partial clearance rates (imiquimod minus vehicle) was 47.3% with a 95% confidence interval of 39.5% to 55.1%. The median percent reduction in AK lesions was 83.3% for the imiquimod group and 0% for the vehicle group. Local skin reactions were common. Severe erythema was reported by 17.7% of participants who received imiquimod and 2.3% of participants who received vehicle. Overall, imiquimod was very well tolerated. Imiquimod 5% cream used 2 times per week for 16 weeks is an effective and well-tolerated treatment for AK.

Comparison of three light doses in the photodynamic treatment of actinic keratosis using mathematical modeling

NASA Astrophysics Data System (ADS)

Vignion-Dewalle, Anne-Sophie; Betrouni, Nacim; Tylcz, Jean-Baptiste; Vermandel, Maximilien; Mortier, Laurent; Mordon, Serge

2015-05-01

Photodynamic therapy (PDT) is an emerging treatment modality for various diseases, especially for cancer therapy. Although high efficacy is demonstrated for PDT using standardized protocols in nonhyperkeratotic actinic keratoses, alternative light doses expected to increase efficiency, to reduce adverse effects or to expand the use of PDT, are still being evaluated and refined. We propose a comparison of the three most common light doses in the treatment of actinic keratosis with 5-aminolevulinic acid PDT through mathematical modeling. The proposed model is based on an iterative procedure that involves determination of the local fluence rate, updating of the local optical properties, and estimation of the local damage induced by the therapy. This model was applied on a simplified skin sample model including an actinic keratosis lesion, with three different light doses (red light dose, 37 J/cm2, 75 mW/cm2, 500 s blue light dose, 10 J/cm2, 10 mW/cm2, 1000 s and daylight dose, 9000 s). Results analysis shows that the three studied light doses, although all efficient, lead to variable local damage. Defining reference damage enables the nonoptimal parameters for the current light doses to be refined and the treatment to be more suitable.

Efficacy and safety of topical SR-T100 gel in treating actinic keratosis in Taiwan: A Phase III randomized double-blind vehicle-controlled parallel trial.

PubMed

Yang, Chao-Chun; Wong, Tak-Wah; Lee, Chih-Hung; Hong, Chien-Hui; Chang, Chung-Hsing; Lai, Feng-Jie; Lin, Shang-Hung; Chi, Ching-Chi; Lin, Tzu-Kai; Yen, Hsi; Wu, Chin-Han; Sheu, Hamm-Ming; Lan, Cheng-Che E

2018-06-01

Currently available topical treatments for actinic keratosis (AK) are associated with substantial side-effects. To evaluate the efficacy and safety of topical SR-T100 gel in treating AK. A multicenter, randomized, double-blinded phase III trial was conducted. Patients with at least two clinically visible AK were enrolled and a punch biopsy was performed on one of the AK to confirm the diagnosis. This study consisted of up to 16-week treatment and 8-week post-treatment periods. Medication was applied daily with occlusive dressing. 123 subjects were recruited and 113 were randomized. 76 subjects were in the SR-T100 and 37 in the vehicle arms. In SR-T100 and vehicle groups, 32.39% and 17.14% of subjects achieved complete clearance, respectively. For 75% partial clearance of lesions, 71.83% and 37.1% of subjects achieved this goal in SR-T100 and vehicle group, respectively. When comparing SR-T100 to vehicle, the odds ratio of complete clearance was 2.14 (p = 0.111), and odds ratio of partial clearance was 4.36 (p < 0.001). Severe local reactions were reported by only one subject using SR-T100. The imitation of the study was that not all the treated AK lesions were confirmed by histopathology. The diagnostic uncertainty may contribute to the high partial clearance rate in the vehicle group since the clinical-diagnosed AK showed higher clearance rate compared to histopathology-confirmed AK. The use of occlusive dressing was another possible explanation for high placebo effects. The results suggested that topical SR-T100 gel may be an effective and safe treatment for field therapy of AK. Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Ingenol mebutate gel for actinic keratosis: the link between quality of life, treatment satisfaction, and clinical outcomes.

PubMed

Augustin, Matthias; Tu, John H; Knudsen, Kim Mark; Erntoft, Sandra; Larsson, Thomas; Hanke, C William

2015-05-01

Actinic keratosis therapy can elicit unsightly and painful local skin responses; assessment of treatment satisfaction and health-related quality of life (QoL) is important. Ingenol mebutate gel is a novel topical field therapy for actinic keratosis. Post-hoc analyses were performed based on patient-reported outcomes from phase-III trials (n = 1005) to assess the effects of ingenol mebutate on QoL and the relationship between both QoL and treatment satisfaction, and degree of lesion clearance. Patients received ingenol mebutate or vehicle for self-application to a 25-cm(2) contiguous area: 0.015% once daily for 3 consecutive days (face/scalp) or 0.05% once daily for 2 consecutive days (trunk/extremities). QoL (Skindex-16) and Treatment Satisfaction Questionnaire for Medication data were recorded. Significant, positive associations between Treatment Satisfaction Questionnaire for Medication score and degree of clearance were identified for patients in the face/scalp (effectiveness P < .0001 and global satisfaction P = .0002) and trunk/extremities (P < .0001 and P = .0014, respectively) groups. There was a significant association between Skindex-16 score and clearance for patients in the face/scalp group for change in symptoms (P = .0218), emotions (P = .0002), and overall Skindex-16 score (P = .0006) from baseline. Clinical trial population findings may not be generalizable to clinical practice. Ingenol mebutate significantly improved patients' QoL and treatment satisfaction. Improvements were associated with higher degrees of actinic keratosis lesion clearance. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Efficacy of Photodynamic Therapy in the Short and Medium Term in the Treatment of Actinic Keratosis, Basal Cell Carcinoma, Acne Vulgaris and Photoaging: Results from Four Clinical Trials

PubMed Central

Martínez-Carpio, PA; Alcolea-López, JM; Vélez, M

2012-01-01

Objective: To determine the clinical efficacy of methyl-aminolevulinate (MAL)-Photodynamic Therapy (PDT) in the treatment of actinic keratosis (AK), basal cell carcinoma (BCC), acne vulgaris (AV) and photoaging (PA), in the short and medium term. Subjects and methods: Four separate prospective studies were designed on patients with AK (n=25), BCC (n=20), AV (n=20) and PA (n=25). Two PDT protocols were applied, and different clinical efficacy criteria were established, including lesion count and size. Two semi-quantitative and four analogue visual scales were completed for the evaluation of results according to the therapist, the patient and two independent experts. Results: In the AK and BCC studies, full clinical remission was observed in 84.7% and 75.7% of lesions, respectively. In the AV study, the number of inflammatory and non-inflammatory lesions fell significantly (p<0.001, p<0.05). In the PA study a reduction in Dover scale scores (3.19 vs. 2.14, p<0.001) was proven. The percentages of satisfied or very satisfied patients were: AK=88%, BCC=90%, AV=89% and PA=80%. A year later, none of the AK or BCC lesions had reappeared, and the cases of AV and PA remained stable, with a tendency towards improvement. Conclusion: the MAL-PDT procedures used produced efficacious, safe and satisfactory results in KA, BCC, AV and PA in the short and medium term. PMID:24511190

Histopathological analysis of the therapeutic response to cryotherapy with liquid nitrogen in patients with multiple actinic keratosis.

PubMed

Oliveira, Marina Câmara de; Trevisan, Flávia; Pinto, Clovis Antônio Lopes; Xavier, Célia Antônia; Pinto, Jaqueline Campoi Calvo Lopes

2015-01-01

Actinic keratoses are premalignant lesions of the skin caused by excessive sun exposure. Lesions may become mainly squamous cell carcinoma. Cryotherapy with liquid nitrogen is one of the main treatments. In order to evaluate the response of actinic keratosis to cryotherapy by histopathology, two lesions were selected in each of 14 patients with multiple actinic keratoses. In one lesion a biopsy was performed and in the other lesion a biopsy was performed after cryotherapy. Subsequently, both biopsies were compared histologically. Of the thirteen patients who completed the study, the best results were obtained in lesions undergoing cryotherapy concerning the atypia of keratinocytes, epithelial thickness and corneal layer and lymphocytic infiltrate. Despite the small number of patients, it was concluded that, if performed correctly, cryotherapy has high efficacy in the treatment of actinic keratoses.

Evidence- and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis - International League of Dermatological Societies in cooperation with the European Dermatology Forum - Short version.

PubMed

Werner, R N; Stockfleth, E; Connolly, S M; Correia, O; Erdmann, R; Foley, P; Gupta, A K; Jacobs, A; Kerl, H; Lim, H W; Martin, G; Paquet, M; Pariser, D M; Rosumeck, S; Röwert-Huber, H-J; Sahota, A; Sangueza, O P; Shumack, S; Sporbeck, B; Swanson, N A; Torezan, L; Nast, A

2015-11-01

Actinic keratosis (AK) is a frequent health condition attributable to chronic exposure to ultraviolet radiation. Several treatment options are available and evidence based guidelines are missing. The goal of these evidence- and consensus-based guidelines was the development of treatment recommendations appropriate for different subgroups of patients presenting with AK. A secondary aim of these guidelines was the implementation of knowledge relating to the clinical background of AK, including consensus-based recommendations for the histopathological definition, diagnosis and the assessment of patients. The guidelines development followed a pre-defined and structured process. For the underlying systematic literature review of interventions for AK, the methodology suggested by the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was adapted. All recommendations were consented during a consensus conference using a formal consensus methodology. Strength of recommendations was expressed based on the GRADE approach. If expert opinion without external evidence was incorporated into the reasoning for making a certain recommendation, the rationale was provided. The Guidelines underwent open public review and approval by the commissioning societies. Various interventions for the treatment of AK have been assessed for their efficacy. The consenting procedure led to a treatment algorithm as shown in the guidelines document. Based on expert consensus, the present guidelines present recommendations on the classification of patients, diagnosis and histopathological definition of AK. Details on the methods and results of the systematic literature review and guideline development process have been published separately. International guidelines are intended to be adapted to national or regional

A Network Meta-Analysis of the Relative Efficacy of Treatments for Actinic Keratosis of the Face or Scalp in Europe

PubMed Central

Vegter, Stefan; Tolley, Keith

2014-01-01

Background Several treatments are available for actinic keratosis (AK) on the face and scalp. Most treatment modalities were compared to placebo and therefore little is known on their relative efficacy. Objectives To compare the different treatments for mild to moderate AK on the face and scalp available in clinical practice in Europe. Methods A network meta-analysis (NMA) was performed on the outcome “complete patient clearance”. Ten treatment modalities were included: two 5-aminolaevulinic acid photodynamic therapies (ALA-PDT), applied as gel (BF-200 ALA) or patch; methyl-aminolevulinate photodynamic therapy (MAL-PDT); three modalities with imiquimod (IMI), applied as a 4-week or 16-week course with 5% imiquimod, or a 2–3 week course with 3.75% imiquimod; cryotherapy; diclofenac 3% in 2.5% hyaluronic acid; 0.5% 5-fluorouracil (5-FU); and ingenol mebutate (IMB). The only data available for 5% 5-FU was from one small study and was determined to be too limited to be reliably included in the analysis. For BF-200 ALA and MAL-PDT, data from illumination with narrow-band lights were selected as these are typically used in clinical practice. The NMA was performed with a random-effects Bayesian model. Results 25 trials on 5,562 patients were included in the NMA. All active treatments were significantly better than placebo. BF-200 ALA showed the highest efficacy compared to placebo to achieve total patient clearance. BF-200 ALA had the highest probability to be the best treatment and the highest SUCRA score (64.8% and 92.1%), followed by IMI 5% 4 weeks (10.1% and 74.2%) and 5-FU 0.5% (7.2% and 66.8%). Conclusions This NMA showed that BF-200 ALA, using narrow-band lights, was the most efficacious treatment for mild to moderate AK on the face and scalp. This analysis is relevant for clinical decision making and health technology assessment, assisting the improved management of AK. PMID:24892649

Genomic instability in human actinic keratosis and squamous cell carcinoma

PubMed Central

Cabral, Luciana Sanches; Neto, Cyro Festa; Sanches, José A; Ruiz, Itamar R G

2011-01-01

OBJECTIVE: To compare the repetitive DNA patterns of human actinic keratoses and squamous cell carcinomas to determine the genetic alterations that are associated with malignant transformation. INTRODUCTION: Cancer cells are prone to genomic instability, which is often due to DNA polymerase slippage during the replication of repetitive DNA and to mutations in the DNA repair genes. The progression of benign actinic keratoses to malignant squamous cell carcinomas has been proposed by several authors. MATERIAL AND METHODS: Eight actinic keratoses and 24 squamous cell carcinomas (SCC), which were pair-matched to adjacent skin tissues and/or leucocytes, were studied. The presence of microsatellite instability (MSI) and the loss of heterozygosity (LOH) in chromosomes 6 and 9 were investigated using nine PCR primer pairs. Random Amplified Polymorphic DNA patterns were also evaluated using eight primers. RESULTS: MSI was detected in two (D6S251, D9S50) of the eight actinic keratosis patients. Among the 8 patients who had squamous cell carcinoma-I and provided informative results, a single patient exhibited two LOH (D6S251, D9S287) and two instances of MSI (D9S180, D9S280). Two LOH and one example of MSI (D6S251) were detected in three out of the 10 patients with squamous cell carcinoma-II. Among the four patients with squamous cell carcinoma-III, one patient displayed three MSIs (D6S251, D6S252, and D9S180) and another patient exhibited an MSI (D9S280). The altered random amplified polymorphic DNA ranged from 70% actinic keratoses, 76% squamous cell carcinoma-I, and 90% squamous cell carcinoma-II, to 100% squamous cell carcinoma-III. DISCUSSION: The increased levels of alterations in the microsatellites, particularly in D6S251, and the random amplified polymorphic DNA fingerprints were statistically significant in squamous cell carcinomas, compared with actinic keratoses. CONCLUSION: The overall alterations that were observed in the repetitive DNA of actinic keratoses and

Characterization and Modulation of Proteins Involved in SM Vesication

DTIC Science & Technology

2005-05-01

shown to be the major etiological factor leading to the precancerous stage of actinic keratosis (AK) and to induction and progression of skin cancers...representing a transient regression-prone precancerous stage equivalent to actinic keratosis . To further examine which caspases are apical and

Effectiveness of cross polarized light and fluorescence diagnosis for detection of sub-clinical and clinical actinic keratosis during imiquimod treatment.

PubMed

Ortonne, Jean-Paul; Gupta, Girish; Ortonne, Nicolas; Duteil, Luc; Queille, Catherine; Mallefet, Pascal

2010-07-01

During treatment of actinic keratosis (AK) lesions with imiquimod sub-clinical lesions often become visible. It is, however, unclear whether these sub-clinical lesions would be detectable beforehand. The aim of this pilot study was to compare two techniques, cross polarized light photography (CPL) and fluorescence diagnosis (FD) using methyllevulinic acid and illumination with Wood's lamp for their ability to detect sub-clinical lesions. These findings were also compared with biopsy results taken before and after treatment with imiquimod 5% cream or vehicle. Twelve patients with at least five clinically visible AK lesions in a single contiguous 20 cm(2) area on the head were recruited. Patient eligibility was determined at the screening visit, when they were randomized to treatment. The randomization was 3:1, active to vehicle (nine treated with imiquimod, three with vehicle cream) for a total duration of 24 weeks (six clinic visits). Patients were assessed for baseline AK lesion counts (clinical and sub-clinical) at the screening visit and final counts at week 20. The number of clinically observed AK lesions was significantly lower at week 12 and week 20 compared with baseline following imiquimod treatment versus vehicle. The number of counted lesions were significantly higher using the CPL method compared with clinical counting with imiquimod treatment at baseline (8.3 +/- 3.4 vs 5.8 +/- 1.3; P = 0.027) and week 20 (4.8 +/- 2.4 vs 3.0 +/- 1.7; P = 0.02) but not in the vehicle group. The FD lesion counting method did not show a significant increase in the number of detected lesions compared with clinical analysis in the imiquimod and placebo groups but when comparisons were performed using pooled data (treatments and visits combined) the results were significant. The number of sub-clinical and clinical AK lesions detected during treatment with imiquimod can be better demonstrated using the methods of CPL and FD, but statistical significance was reached only using

Evaluation of the efficacy and tolerability of 0.5% fluorouracil cream and 5% fluorouracil cream applied to each side of the face in patients with actinic keratosis.

PubMed

Loven, Keith; Stein, Linda; Furst, Katharine; Levy, Sharon

2002-06-01

A new 0.5% fluorouracil cream has been developed that provides an alternative to the more highly concentrated topical formulations of fluorouracil that are currently available. This was a comparison of the tolerability and efficacy of the 0.5% and 5% fluorouracil creams in the treatment of actinic keratosis (AK). During this single-blind, randomized study, patients with > or =6 AK lesions were treated for 4 weeks with the 0.5% (once daily) and 5% (twice daily) fluorouracil creams applied to opposite sides of the face. After the end of treatment, patients were followed for an additional 4 weeks. Efficacy variables included absolute and percent reductions in AK lesions from baseline and total clearance of AK lesions. A questionnaire was used to evaluate patients' treatment preferences. Tolerability was evaluated through continuous monitoring of adverse events. Treatment with 0.5% fluorouracil cream reduced the number of AK lesions from 11.3 at baseline to 2.5 at the end of the 4-week follow-up phase, compared with a reduction from 10.3 to 4.2 lesions after treatment with 5% fluorouracil cream. The reduction was significantly greater with the 0.5% cream compared with the 5% cream (P = 0.044). The 0.5% cream was as effective as the 5% cream in terms of the percent reduction in AK lesions from baseline (67% and 47%, respectively) and in achieving total clearance of AK lesions (both treatments, approximately 43% of patients). Both treatments were associated with similar degrees of investigator-rated irritation; however, patients preferred the 0.5% cream because they felt it was more tolerable (P = 0.003), easier to apply, and had a once-daily application schedule. Although all patients experienced facial irritation in association with both creams, fewer patients treated with the 0.5% cream reported symptoms of facial irritation. In this study, 0.5% fluorouracil cream once daily was at least as effective as 5% fluorouracil cream twice daily in terms of the percent

Dermatoscopic Findings of Seborrheic Keratosis in Melanoma.

PubMed

Brandão, Maria Luiza; Oliveira Lima, Cíntia Maria; Moura, Heloísa Helena; Ishida, Cleide; Campos-do-Carmo, Gabriella; Cuzzi, Tullia; Ramos-E-Silva, Marcia

2016-06-01

Cutaneous melanoma may in some instances be confused with seborrheic keratosis, which is a very common neoplasia, more often mistaken for actinic keratosis and verruca vulgaris. Melanoma may clinically resemble seborrheic keratosis and should be considered as its possible clinical simulator. We report a case of melanoma with dermatoscopic characteristics of seborrheic keratosis and emphasize the importance of the dermatoscopy algorithm in differentiating between a melanocytic and a non-melanocytic lesion, of the excisional biopsy for the establishment of the diagnosis of cutaneous tumors, and of the histopathologic examination in all surgically removed samples.

Pharmacoeconomy of drugs used in the treatment of actinic keratoses

PubMed Central

Nisticò, S; Torchia, V; Gliozzi, M; Bottoni, U; Del Duca, E; Muscoli, C

2016-01-01

Actinic keratosis (AK) represents an emerging issue in the area of skin diseases which undergo high risk for developing squamous cell carcinoma (SCC). Recently, evidence has been accumulated that 3% diclofenac sodium and ingenol mubetate may efficiently counteract the development of progressive AK even if the pharmacoeconomic impact of such a treatment remains poorly defined. With the objective of assessing the efficacy of 3% diclofenac sodium versus ingenol mebutate, a comparative cost-efficacy analysis was performed between both pharmacological treatments. In the present analysis, data of efficacy of clinical studies were combined with information on the quality of life associated with AK lesions based on available literature data. Furthermore, the cost associated with the management of these lesions in Italy has been taken into account. To this purpose, we carried out a literature survey on the clinical and economic data among clinical reports available in Italy based on the assessment of related expenditure of public resources and their relationship with the subsequent health benefits. PMID:27207444

Italian guidelines and therapeutic algorithm for actinic keratoses.

PubMed

Rossi, R; Calzavara-Pinton, P G; Giannetti, A; Peserico, A; Santucci, M; Vena, G A; Lotti, T

2009-12-01

The prevalence of actinic keratosis (AK) continues to rise among white people throughout the world and it is necessary to increase the level of attention paid to it from a diagnostic and a preventive point of view. Today, AK must be considered an in situ squamous cell carcinoma and as such, must be managed using one of the available approved therapeutic alternatives. However, when multiple AKs develop on severely photodamaged skin, the treatment of the lesion together with that of the field of cancerization is part of an optimal strategy that aims not only to solve alterations clinically evident but also those in the surrounding skin field cancerization, that most likely hosts genetic alterations and is the site of initial gradual replacement of normal cells with tumoral cells. This paper reports the most recent evidences from a careful review of the literature's key articles of the treatment of AKs and suggests guidelines for the clinicians. The guidelines indicated by the authors have also been based on practical evaluations and their own clinical experience. The present conclusions may be modified by new findings in the field of oncologic research.

[Immunohistochemical study of the specific features of expression of matrix metalloproteinases 1, 9 in the photoaged skin, the foci of actinic keratosis and basal cell carcinoma].

PubMed

Kuznetsova, E V; Snarskaya, E S; Zavalishina, L E; Tkachenko, S B

Matrix metalloproteinases (MMPs) mediate the degradation of all types of collagens and other extracellular matrix components (elastin, proteoglycans, and laminin), their synthesis and accumulation play a key role in the hydrolysis of basement membrane. MMPs are involved in a wide range of proteolytic processes in the presence of different physiological and pathological changes, including inflammation, wound healing, angiogenesis, and carcinogenesis. to study the specific features of MMP-1 and MMP-9 expression in different stages of skin photoaging, in the foci of actinic keratosis and basal cell carcinoma by immunohistochemical examination. 12 samples of the healthy skin (6 samples of the eyelid skin with Glogau grade II photoaging; 6 ones of eyelid skin with Glogau grades III-IV photoaging) and biopsies from 8 foci of actinic keratosis and from 8 ones of basal cell carcinoma were examined. A positive reaction to MMPs was shown as different brown staining intensity in the cytoplasm of keratinocytes/tumor cells. MMP-1 and MMP-9 expression was recorded in 67% of the histological specimens of the Glogau grade III photoaged skin and in 100% of those of Glogau grade IV. In the foci of actinic keratosis, the expression of MMP-1 was observed in 62.5% of cases and that of MMP-9 was seen in 87.5%. In basal cell carcinoma, the expression of MMP-1 and MMP-9 was detected in all investigated samples. The immunomorphological findings are indicative of the important role of the level of MMP-1 and MMP-9 expression that is associated with the degree of progression of skin photoaging processes. Minimal MMP-1 and MMP-9 expression was recorded even in grades III-IV photoaging and in the foci of actinic keratosis. Intense MMP-1 and MMP-9 expression was detected in malignant skin epithelial neoplasms as different clinicomorphological types of basal cell carcinoma.

A randomized pilot comparative study of topical methyl aminolevulinate photodynamic therapy versus imiquimod 5% versus sequential application of both therapies in immunocompetent patients with actinic keratosis: clinical and histologic outcomes.

PubMed

Serra-Guillén, Carlos; Nagore, Eduardo; Hueso, Luis; Traves, Victor; Messeguer, Francesc; Sanmartín, Onofre; Llombart, Beatriz; Requena, Celia; Botella-Estrada, Rafael; Guillén, Carlos

2012-04-01

Photodynamic therapy (PDT) and imiquimod are the treatments of choice for actinic keratosis (AK). As they have different mechanisms of action, it seems reasonable to assume that applying both treatments sequentially would be efficacious. We sought to determine which of these therapeutic modalities provides a better clinical and histologic response in patients with AK and whether sequential use of both was more efficacious than each separately. Patients were randomly assigned to one treatment group: group 1, PDT only; group 2, imiquimod only; or group 3, sequential use of PDT and imiquimod. The primary outcome measure was complete clinical response. Partial clinical response was defined as a reduction of more than 75% in the initial number of lesions. A complete clinicopathologic response was defined as lack of evidence of AK in the biopsy specimen. In all, 105 patients completed the study (group 1, 40 patients; group 2, 33 patients; group 3, 32 patients). Sequential application of PDT and imiquimod was more efficacious in all the outcome measures. More patients were satisfied with PDT than with the other two modalities (P = .003). No significant differences were observed among the 3 modalities and tolerance to treatment. Only one cycle of imiquimod was administered. The follow-up period was brief. Sequential application of PDT and imiquimod provides a significantly better clinical and histologic response in the treatment of AK than PDT or imiquimod monotherapy. It also produces less intense local reactions and better tolerance and satisfaction than imiquimod monotherapy. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Spanish-Portuguese consensus statement on use of daylight-mediated photodynamic therapy with methyl aminolevulinate in the treatment of actinic keratosis.

PubMed

Gilaberte, Y; Aguilar, M; Almagro, M; Correia, O; Guillén, C; Harto, A; Pérez-García, B; Pérez-Pérez, L; Redondo, P; Sánchez-Carpintero, I; Serra-Guillén, C; Valladares, L M

2015-10-01

Daylight-mediated photodynamic therapy (PDT) is a new type of PDT that is as effective as conventional PDT in grade 1 and 2 actinic keratosis but with fewer adverse effects, resulting in greater efficiency. The climatic conditions in the Iberian Peninsula require an appropriately adapted consensus protocol. We describe a protocol for the treatment of grade 1 and 2 actinic keratosis with daylight-mediated PDT and methyl aminolevulinate (MAL) adapted to the epidemiological and clinical characteristics of Spanish and Portuguese patients and the climatic conditions of both countries. Twelve dermatologists from different parts of Spain and Portugal with experience in the treatment of actinic keratosis with PDT convened to draft a consensus statement for daylight-mediated PDT with MAL in these countries. Based on a literature review and their own clinical experience, the group developed a recommended protocol. According to the recommendations adopted, patients with multiple grade 1 and 2 lesions, particularly those at risk of developing cancer, are candidates for this type of therapy. Daylight-mediated PDT can be administered throughout the year, although it is not indicated at temperatures below 10°C or at excessively high temperatures. Likewise, therapy should not be administered when it is raining, snowing, or foggy. The procedure is simple, requiring application of a sunscreen with a protection factor of at least 30 based exclusively on organic filters, appropriate preparation of the lesions, application of MAL without occlusion, and activation in daylight for 2hours. This consensus statement represents a practical and detailed guideline to achieve maximum effectiveness of daylight-mediated PDT with MAL in Spain and Portugal with minimal adverse effects. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

Dermoscopy of Pigmented Actinic Keratosis of the Face: A Study of 232 Cases.

PubMed

Kelati, A; Baybay, H; Moscarella, E; Argenziano, G; Gallouj, S; Mernissi, F Z

2017-11-01

The diagnosis of pigmented actinic keratosis (PAK) is often challenging because of overlapping features with lentigo maligna. To investigate dermoscopic patterns of PAK according to their different evolutionary stages, and to correlate the pattern with clinical characteristics of the patients. Descriptive and analytical study of 232 PAK. Dermoscopic patterns were divided into two categories: the follicule surroundings' abnormalities (FSA) and follicular keratosis' abnormalities (FKA). FSA and FKA dermoscopic patterns were related to male gender, except for star-like appearance, double white clods and dermoscopic horn (p≤0.04). Rhomboidal, annular granular pattern, gray halo, white circle and double clods were dermoscopic pattern significantly related to xeroderma pigmentosum's type of skin. Based on the evolutionary stages of PAK, the jelly sign was significantly related to thin patches of PAK. Central crusts and scales were related to thick plaques and the star-like appearance to hypertrophic PAK. The presence of 2 or more dermoscopic signs in both FSA and FKA was noticed in 99.1% of lesions. The dermoscopic diagnosis of PAK vary according to the evolutionary stages of the disease, this will increase the diagnosis accuracy, with therapeutic implications. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Long-term Efficacy of Topical Fluorouracil Cream, 5%, for Treating Actinic Keratosis: A Randomized Clinical Trial.

PubMed

Pomerantz, Hyemin; Hogan, Daniel; Eilers, David; Swetter, Susan M; Chen, Suephy C; Jacob, Sharon E; Warshaw, Erin M; Stricklin, George; Dellavalle, Robert P; Sidhu-Malik, Navjeet; Konnikov, Nellie; Werth, Victoria P; Keri, Jonette; Lew, Robert; Weinstock, Martin A

2015-09-01

Topical fluorouracil was demonstrated to be effective in reducing the number of actinic keratoses (AKs) for up to 6 months, but no randomized trials studied its long-term efficacy. To evaluate the long-term efficacy of a single course of fluorouracil cream, 5%, for AK treatment. The Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) trial was a randomized, double-blinded, placebo-controlled trial with patients from dermatology clinics at 12 VA medical centers recruited from 2009 to 2011 and followed up until 2013. Our study population comprised 932 veterans with 2 or more keratinocyte carcinomas in the 5 years prior to enrollment. The mean follow-up duration was 2.6 years in both treatment and control groups. Participants applied either topical fluorouracil cream, 5% (n = 468), or vehicle control cream (n = 464) to the face and ears twice daily for up to 4 weeks. This study reports on AK counts and treatments, which were secondary outcomes of the VAKCC trial. Actinic keratoses on the face and ears were counted by study dermatologists at enrollment and at study visits every 6 months. The number of spot treatments for AKs on the face and ears at semiannual study visits and in between study visits was recorded. The number of AKs on the face and ears per participant was not different between the fluorouracil and control groups at randomization (11.1 vs 10.6, P > .10). After randomization, the fluorouracil group had fewer AKs compared with the control group at 6 months (3.0 vs 8.1, P < .001) and for the overall study duration (P < .001). The fluorouracil group also had higher complete AK clearance rates (38% vs 17% at 6 months) and fewer spot treatments at 6-month intervals, at study visits, and in between study visits during the trial (P < .01 for all). The fluorouracil group took longer to require the first spot AK treatment (6.2 months) compared with the control group (6.0 months) (hazard ratio, 0.69; 95% CI, 0.60-0.79). The

Treatment of Grade II and III Actinic Keratosis Lesions with a Film-Forming Medical Device Containing Sunscreen/Piroxicam 0.8% and a Retinoic Acid/Glycolic Gel: A Pilot Trial.

PubMed

Puviani, Mario; Milani, Massimo

2018-05-31

Lesion and field-targeted treatments of actinic keratosis (AK) are commonly indicated for grade I and II type lesions. Grade III lesions are in general more difficult to treat. A film-forming medical device containing piroxicam 0.8% and sunscreen (SPF 50+) (PS) has been shown to be effective in the treatment of grade I and II AK lesions. Topical and oral retinoids have been utilized in AK and non-melanoma skin cancers. Topical glycolic acid promotes keratolysis and stimulates collagen synthesis for repair and skin rejuvenation and could be useful in AK treatment strategies. A gel containing retinoid acid (0.02%) and glycolic acid (4%) (RC) is commercially available. The objective of the study was to evaluate the efficacy and local tolerability of a combined treatment approach with PS and RC in subjects with multiple grade II and III AK lesions. Twenty-two subjects (16 males and 6 females; mean age 68 years) with more than five AK lesions were enrolled after obtaining their informed consent in a 3-month trial. PS cream was applied twice daily every day and RC gel was applied twice daily for 2 consecutive days every week. The primary endpoint was the evolution of the AK mean number from baseline to the end of the trial. Secondary endpoints were the thickness of the target lesion (expressed in mm 3 ) and the erythema score (hemoglobin content), evaluated using a standardized computer-based image acquisition analysis system (Anthera 3D). At baseline, the mean (SD) lesion number was 7.7 (3) for grade II and 1.4 (1) for grade III AK. At the end of the study, a significant (P = 0.001) reduction was observed for both grade II (- 81%; from 7.7 to 1.5) and grade III (- 22%) lesions. Six grade III lesions out of 31 (20%), presented at baseline, completely disappeared at month 3. For grade III lesions, a significant mean thickness reduction of 51% was observed at month 3. The erythema score (all lesions) was reduced by 70%. Four patients out of 22 (18%) were

Automated Detection of Actinic Keratoses in Clinical Photographs

PubMed Central

Hames, Samuel C.; Sinnya, Sudipta; Tan, Jean-Marie; Morze, Conrad; Sahebian, Azadeh; Soyer, H. Peter; Prow, Tarl W.

2015-01-01

Background Clinical diagnosis of actinic keratosis is known to have intra- and inter-observer variability, and there is currently no non-invasive and objective measure to diagnose these lesions. Objective The aim of this pilot study was to determine if automatically detecting and circumscribing actinic keratoses in clinical photographs is feasible. Methods Photographs of the face and dorsal forearms were acquired in 20 volunteers from two groups: the first with at least on actinic keratosis present on the face and each arm, the second with no actinic keratoses. The photographs were automatically analysed using colour space transforms and morphological features to detect erythema. The automated output was compared with a senior consultant dermatologist’s assessment of the photographs, including the intra-observer variability. Performance was assessed by the correlation between total lesions detected by automated method and dermatologist, and whether the individual lesions detected were in the same location as the dermatologist identified lesions. Additionally, the ability to limit false positives was assessed by automatic assessment of the photographs from the no actinic keratosis group in comparison to the high actinic keratosis group. Results The correlation between the automatic and dermatologist counts was 0.62 on the face and 0.51 on the arms, compared to the dermatologist’s intra-observer variation of 0.83 and 0.93 for the same. Sensitivity of automatic detection was 39.5% on the face, 53.1% on the arms. Positive predictive values were 13.9% on the face and 39.8% on the arms. Significantly more lesions (p<0.0001) were detected in the high actinic keratosis group compared to the no actinic keratosis group. Conclusions The proposed method was inferior to assessment by the dermatologist in terms of sensitivity and positive predictive value. However, this pilot study used only a single simple feature and was still able to achieve sensitivity of detection of 53

Clinical Response to Ingenol Mebutate in Patients With Actinic Keratoses.

PubMed

Batalla, A; Flórez, Á; Feal, C; Peón, G; Abalde, M T; Salgado-Boquete, L; de la Torre, C

2015-12-01

Cryotherapy is the most common treatment for actinic keratosis, but its effect is limited to individual lesions. Several topical drugs, however, are available that, in addition to treating individual actinic keratoses, target field cancerization and thereby act on subclinical lesions. Examples are 5-fluorouracil, imiquimod, diclofenac, and ingenol mebutate. We report on 17 patients with actinic keratoses treated with ingenol mebutate and describe our findings on treatment effectiveness, adherence, and tolerance. Complete and partial response rates were 35% and 53%, respectively. Ninety-four percent of patients fully adhered to treatment and 18% developed severe local reactions. Ingenol mebutate is an effective treatment for actinic keratosis. Although it has a similar rate of local reactions to other treatments available for actinic keratosis, its short treatment regimen favors better adherence. Copyright © 2014 Elsevier España, S.L.U. y AEDV. All rights reserved.

Efficacy of ablative fractional laser-assisted photodynamic therapy with short-incubation time for the treatment of facial and scalp actinic keratosis: 12-month follow-up results of a randomized, prospective, comparative trial.

PubMed

Choi, S H; Kim, K H; Song, K H

2015-08-01

Photodynamic therapy (PDT) using methyl aminolevulinate (MAL) is an effective first-line treatment for actinic keratosis (AK). Erbium:yttrium-aluminium-garnet (Er:YAG) ablative fractional laser-assisted MAL-PDT (AFL-PDT) has shown significant benefit for the treatment of AK. The objectives of this study were to compare the efficacy, recurrence rate, cosmetic outcome and safety between AFL-PDT with 2 and 3 h of incubation vs. Conventional MAL-PDT in patients with facial and scalp AK. This prospective randomized trial initially enrolled 440 facial and scalp AK lesions in 93 patients. Patients were randomly assigned to AFL-PDT with a 2-h incubation time (2h-AFL-PDT), 3h-AFL-PDT and 3h-MAL-PDT. All patients underwent one session of MAL-PDT using a red light-emitting diode lamp at 37 J/cm(2) , and AFL-PDT groups were assigned to pretreatment with Er:YAG AFL. Patients were followed up at 1 week, 3 months and 12 months post treatment. Efficacy, cosmetic outcomes and adverse events were assessed. Finally, 427 facial AK lesions in 88 patients were analysed in this study. Three months after the last treatment session, 3h-AFL-PDT (91.7%) was significantly more effective than 2h-AFL-PDT (76.8%) and 3h-MAL-PDT (65.6%, P < 0.001), and differences in efficacy remained significant at the 12-month follow-up. The recurrence rate was significantly lower for 3h-AFL-PDT (7.5%) than for 3h-MAL-PDT (22.1%) at 12 months (P = 0.002);however, no significant difference was found between 2h-AFL-PDT and 3h-MAL-PDT. No significant difference was found in cosmetic outcomes or safety between the three groups. We recommend 3h-AFL-PDT rather than classic MAL-PDT or short-incubation AFL-PDT for treating AK. © 2015 European Academy of Dermatology and Venereology.

Efficacy of iontophoresis-assisted ablative fractional laser photodynamic therapy with short incubation time for the treatment of actinic keratosis: 12-month follow-up results of a prospective, randomised, comparative trial.

PubMed

Choi, Seung-Hwan; Kim, Tae-Hoon; Song, Ki-Hoon

2017-06-01

Iontophoresis is a transdermal drug-delivery technique that enhances the transport of ionic species across membranes and may have significant benefit for the treatment of actinic keratosis (AK) by ablative fractional laser-primed photodynamic therapy (AFL-PDT). The aims of this study were to compare the efficacy, recurrence rate, cosmetic outcome and safety of iontophoresis-assisted AFL-PDT with 2h of incubation vs. those of conventional AFL-PDT with 2- and 3-h incubation in patients with facial and scalp AK. Patients were randomly assigned to iontophoresis-assisted AFL-PDT with a 2-h incubation time (group A) and conventional AFL-PDT with a 2-h (group B) and 3-h (group C) incubation time. All patients underwent AFL-PDT, and group A patients were assigned to treatment with iontophoresis after methyl-aminolevulinate (MAL) application. After 2 or 3h, MAL-applied lesions were irradiated using a red light. Patients were followed up at 1-week, 3 months and 12 months after treatment. Efficacy, cosmetic outcomes and adverse events were assessed. In total, 41 patients (160 AK lesions) completed the study and were evaluated. Efficacy was significantly higher in Group A (88.7%) than in Group B (73.2%); the efficacy of groups A and C (92.2%) at 3 months follow-up was comparable. The recurrence rates were not significantly different between the groups at 12 months (P=0.841). The three groups did not differ in terms of cosmetic outcomes and safety. Iontophoresis-assisted AFL-PDT showed higher efficacy than AFL-PDT with short incubation time. Iontophoresis may effectively reduce the incubation time in AFL-PDT. Copyright © 2017 Elsevier B.V. All rights reserved.

Management of actinic keratosis.

PubMed

2013-07-01

Actinic keratoses are common, often multiple, epidermal lesions found mainly on the sun-exposed skin of fair-skinned middle-aged and older people.(1) Over time, lesions may remain unchanged or may proliferate, regress, reappear or develop into squamous cell carcinoma (SCC).(2) Detectable (spot) lesions are often associated with alteration of the surrounding skin (field) where subclinical lesions might be present.(2) Interventions may target individual or multiple lesions or a whole field.(2) Here, we update our previous review(3) on the prevention and treatment of actinic keratoses, focusing on the licensed treatments most commonly used in the UK and recommended in UK guidelines.

Swiss clinical practice guidelines on field cancerization of the skin.

PubMed

Hofbauer, Günther; Anliker, Mark; Boehncke, Wolf-Henning; Brand, Christoph; Braun, Ralph; Gaide, Olivier; Hafner, Jürg; Hunger, Robert; Itin, Peter; Kaeuper, Gina; Lautenschlager, Stephan; Mainetti, Carlo; Streit, Markus

2014-01-01

Actinic keratosis (AK) affects millions of people worldwide, and its prevalence continues to increase. AK lesions are caused by chronic ultraviolet radiation exposure, and the presence of two or more AK lesions along with photodamage should raise the consideration of a diagnosis of field cancerization. Effective treatment of individual lesions as well as field cancerization is essential for good long-term outcomes. The Swiss Registry of Actinic Keratosis Treatment (REAKT) Working Group has developed clinical practice guidelines for the treatment of field cancerization in patients who present with AK. These guidelines are intended to serve as a resource for physicians as to the most appropriate treatment and management of AK and field cancerization based on current evidence and the combined practical experience of the authors. Treatment of AK and field cancerization should be driven by consideration of relevant patient, disease, and treatment factors, and appropriate treatment decisions will differ from patient to patient. Prevention measures and screening recommendations are discussed, and special considerations related to management of immunocompromised patients are provided.

Tumor-Preferential Induction of Immune Responses and Epidermal Cell Death in Actinic Keratoses by Ingenol Mebutate

PubMed Central

Zibert, John R.; Schön, Margarete; Hald, Andreas; Hansen, Maria H.; Litman, Thomas; Schön, Michael P.

2016-01-01

The rapid and strong clinical efficacy of the first-in-class, ingenol mebutate, against actinic keratosis (AK) has resulted in its recent approval. We conducted the first comprehensive analysis of the cellular and molecular mode of action of topical ingenol mebutate 0.05% gel in both AK and uninvolved skin of 26 patients in a phase I, single-center, open-label, within-patient comparison. As early as 1 day after application, ingenol mebutate induced profound epidermal cell death, along with a strong infiltrate of CD4+ and CD8+ T-cells, neutrophils, and macrophages. Endothelial ICAM-1 activation became evident after 2 days. The reaction pattern was significantly more pronounced in AK compared with uninvolved skin, suggesting a tumor-preferential mode of action. Extensive molecular analyses and transcriptomic profiling of mRNAs and microRNAs demonstrated alterations in gene clusters functionally associated with epidermal development, inflammation, innate immunity, and response to wounding. Ingenol mebutate reveals a unique mode of action linking directly to anti-tumoral effects. Trial Registration: ClinicalTrials.gov NCT01387711 PMID:27612149

Use of reflectance confocal microscopy to evaluate 5-fluorouracil 0.5%/salicylic acid 10% in the field-directed treatment of subclinical lesions of actinic keratosis: subanalysis of a Phase III, randomized, double-blind, vehicle-controlled trial.

PubMed

Ulrich, M; Reinhold, U; Falqués, M; Rodriguez Azeredo, R; Stockfleth, E

2018-03-01

Actinic keratosis (AK) is a common skin disorder that can progress to invasive squamous-cell carcinoma. AK can present as clinical (visible) or subclinical (invisible) lesions within areas of chronic sun damage. The importance of treating subclinical AK is gaining support. We present a subanalysis of a previously published Phase III, double-blind, vehicle-controlled study (NCT02289768), to assess 5-fluorouracil (5-FU) 0.5%/salicylic acid 10% treatment of subclinical AK lesions, based on reflectance confocal microscopy (RCM). To determine the efficacy of 5-FU 0.5%/salicylic acid 10% as field-directed treatment for subclinical AK lesions using RCM. For inclusion in this subanalysis, patients had to have at least three subclinical AK lesions within a 25 cm 2 area of skin. Subclinical AK lesions were diagnosed according to the presence of three key RCM criteria: architectural disarray; keratinocyte atypia and pleomorphism at the basal, spinous and granular layer. Subclinical AK lesions were evaluated by RCM at baseline, after 4, 6 and 12 weeks of 5-FU 0.5%/salicylic acid 10% treatment or vehicle, and 8 weeks following the end of treatment. Twenty-seven patients were included: 17 [mean age = 72.2 years, standard deviation (SD) = 6.3] received 5-FU 0.5%/salicylic acid 10% treatment and 10 (mean age = 76.4 years, SD = 3.9) received vehicle. Eight weeks following the end of treatment, the mean number of subclinical lesions declined (from 3.0 at baseline) to 0.3 (95% confidence interval [CI] 0.06-0.57) for the 5-FU 0.5%/salicylic acid 10% group and 1.6 (95% CI 0.52-2.68) in the vehicle group (reductions of 90% [95% CI 72.1-107.1] vs. 47% [95% CI 24.8-69.5], respectively; P = 0.005). The proportion of patients receiving 5-FU 0.5%/salicylic acid 10% showing complete clearance of three preselected subclinical AK lesions was numerically greater than in the vehicle group (69% vs. 40%, respectively; P = 0.183). To the best of our knowledge, this is the first randomized, vehicle

Efficacy of a film-forming medical device containing sunscreen (50+) and piroxicam 0.8% in actinic keratosis and field cancerization: a multicenter, assessor-blinded, 3 month trial.

PubMed

Puviani, Mario; Galloni, Chiara; Marchetti, Silvia; Sergio Pavone, Paolo; Lovati, Silvia; Pistone, Giuseppe; Caputo, Valentina; Tilotta, Giovanna; Scarcella, Giuseppe; Campione, Elena; Diluvio, Laura; Garofalo, Virginia; Bianchi, Luca; Milani, Massimo

2017-07-01

Sunscreen protection in subjects with actinic keratosis (AK) is highly recommended to prevent clinical evolution of this in situ skin cancer condition. Use of topical anti-cyclooxygenase drugs such as diclofenac and piroxicam reduces the number of lesions and improves the cancerization field. A film-forming medical device in a cream formulation containing organic and inorganic sun-filters (50+ SPF) and piroxicam 0.8% (ACTX) has shown in a pilot, single-center, open trial to reduce AK lesions improving the cancerization field. We evaluated in a multicenter, assessor-blinded, 3 month trial the efficacy of ACTX in AK. A total of 70 subjects with at least three AK lesions on the scalp or face were enrolled after written informed consent. Primary outcomes of the study were the clinical evolution of number of AK lesions on a target zone area and the evolution of dermoscopy features of the target lesion, assessing erythema, scaling, pigmentation, and follicular plug, using a 5 point score (from 0 to 4; maximum score: 16). Lesion count and dermoscopy score were evaluated in a blind fashion assessing digital color high definition coded images. A secondary outcome was the Investigator Global Score (IGS) of clinical evolution of the target area using a 7 point scale from -2 (significantly worse) to +4 (completely cured). IGS was evaluated in an open fashion. Subjects were instructed to apply the cream twice daily on the target area, using one finger-tip unit for the treatment of a 35 cm 2 area. All but one subject (40 men and 30 women, mean age 73 years) concluded the study period. At baseline the mean (±SD) number of AK lesions in the target area were 7.0 (5.9) with a median value of 5 and the dermoscopy score of the target lesion was 7.0 (2.3) with a median value of 7.0. ACTX treatment reduced AK lesions to 3.2 (2.9), (p = .0001; Wilcoxon Test), representing a 55% relative reduction. Dermoscopy score was reduced to 3.3 (2.6) (p = .0001) (a reduction of 53%). The

Number of Langerhans cells is decreased in premalignant keratosis and skin cancers.

PubMed

Shevchuk, Z; Filip, A; Shevchuk, V; Kashuba, E

2014-03-01

It was shown earlier that a number of CD207 positive Langerhans cells was lower in basal cell carcinomas than in the normal epidermis. Moreover, benign skin lesions presented a higher number of Langerhans cells when they were compared to malignant tumors. To count Langerhans cells, assessing expression levels of CD1A and CD207 markers in actinic keratosis, basal and squamous cell carcinomas, compared with the normal skin. Comparison of Langerhans cells might give a valuable prognostic marker for skin cancer. Immunohistochemistry and methods of statistics were used. Expression of CD1A and CD207 markers was assessed in tumor samples of actinic keratosis, cutaneous basal and squamous cell carcinomas, in comparison with the normal skin. In each cohort there were 40 patients (and 11 healthy individuals). We have shown that the number of Langerhans cells is considerably lower in cutaneous basal and squamous cell carcinomas, compared with their number in the normal skin (p < 0.0001). CD1A expression correlated with CD207 expression only in the control group. There was no correlation in actinic keratosis, basal and squamous cell carcinoma. This may suggest an alteration of Langerhans cells phenotype in skin neoplastic diseases, making the number of Langerhans cells a valuable prognostic factor for skin tumors.

Long-term (6 and 12 months) follow-up of two prospective, randomized, controlled phase III trials of photodynamic therapy with BF-200 ALA and methyl aminolaevulinate for the treatment of actinic keratosis

PubMed Central

Dirschka, T; Radny, P; Dominicus, R; Mensing, H; Brüning, H; Jenne, L; Karl, L; Sebastian, M; Oster-Schmidt, C; Klövekorn, W; Reinhold, U; Tanner, M; Gröne, D; Deichmann, M; Simon, M; Hübinger, F; Hofbauer, G; Krähn-Senftleben, G; Borrosch, F; Reich, K; Berking, C; Wolf, P; Lehmann, P; Moers-Carpi, M; Hönigsmann, H; Wernicke-Panten, K; Hahn, S; Pabst, G; Voss, D; Foguet, M; Schmitz, B; Lübbert, H; Szeimies, R-M

2013-01-01

Background Two phase III trials of photodynamic therapy (PDT) with BF-200 ALA, a recently approved nanoemulsion formulation of 5-aminolaevulinic acid (ALA) demonstrated high clearance rates in mild-to-moderate actinic keratosis (AK). The comparison to a registered methyl aminolaevulinate (MAL) cream demonstrated significantly superior total patient clearance rates. Objectives To evaluate long-term efficacy and safety of PDT for AK 6 and 12 months after the last PDT with BF-200 ALA, MAL or placebo. Methods The follow-up phase (FUP) was performed with patients of two phase III studies. Both studies compared BF-200 ALA with placebo, one of the studies additionally with MAL. Overall recurrence rates and various subgroups (light source, lesion severity, lesion location, complete responders after first PDT) were assessed 6 and 12 months after the last PDT. Results Recurrence rates were similar for BF-200 ALA and MAL, with a tendency to lower recurrence rates for BF-200 ALA. The proportion of patients who were fully cleared during PDT and remained completely clear for at least 12 months after PDT were 47% for BF-200 ALA (both studies) and 36% for MAL treatment. The subgroup that was illuminated with narrow wavelength LED lamps reached 69% and 53% for BF-200 ALA (both studies, respectively) and 41% for MAL. No safety concerns were reported. Conclusions The FUP data confirmed the high efficacy and safety of PDT with BF-200 ALA. The slightly lower recurrence rates after BF-200 ALA treatment compared with MAL treatment enhanced the better treatment outcome due to the significantly superior efficacy. PMID:23252768

Photodynamic therapy is more effective than imiquimod for actinic keratosis in organ transplant recipients: a randomized intraindividual controlled trial.

PubMed

Togsverd-Bo, K; Halldin, C; Sandberg, C; Gonzalez, H; Wennberg, A M; Sørensen, S S; Wulf, H C; Haedersdal, M

2018-04-01

Actinic keratoses (AKs) in solid organ transplant recipients (OTRs) are difficult-to-treat premalignancies and comparison of topical therapies is therefore warranted. In an intraindividual study to compare the efficacy and safety of field treatment with methyl aminolaevulinate photodynamic therapy (MAL-PDT) and imiquimod (IMIQ) for AKs in OTRs. OTRs (n = 35) with 572 AKs (grade I-III) in two similar areas on the face, scalp, dorsal hands or forearms were included. All patients received one MAL-PDT and one IMIQ session (three applications per week for 4 weeks) in each study area according to randomization. Treatments were repeated after 2 months (IMIQ) and 3 months (PDT) in skin with incomplete AK response. Outcome measures were complete lesion response (CR), skin reactions, laboratory results and treatment preference. The majority of study areas received two treatment sessions (PDT n = 25 patients; IMIQ n = 29 patients). At 3 months after two treatments, skin treated with PDT achieved a higher rate of CR (AK I-III median 78%; range 50-100) compared with IMIQ-treated skin areas (median 61%, range 33-100; P < 0·001). Fewer emergent AKs were seen in PDT-treated skin vs. IMIQ-treated skin (0·7 vs. 1·5 AKs, P = 0·04). Patients developed more intense inflammatory skin reactions following PDT, which resolved more rapidly compared with IMIQ (median 10 days vs. 18 days, P < 0·01). Patient preference (P = 0·47) and cosmesis (P > 0·30) were similar for PDT and IMIQ. Compared with IMIQ, PDT treatment obtained a higher rate of AK clearance at 3-month follow-up and achieved shorter-lasting, but more intense, short-term skin reactions. © 2017 British Association of Dermatologists.

Actikerall™ (5-Fluorouracil 0.5% and Salicylic Acid 10%) Topical Solution for Patient-directed Treatment of Actinic Keratoses.

PubMed

Nguyen, H P; Rivers, J K

2016-05-01

Actinic keratosis (AK), a common cutaneous lesion with the potential to transform into squamous cell carcinoma, has traditionally been treated with ablative and/or surgical procedures. Recently, a topical formulation combining 0.5% 5-fluorouracil with 10% salicylic acid (5-FU-SA) was introduced in Europe under the trade name Actikerall™ for the treatment of grade I/II AKs. In a single randomized phase III trial, 5-FU-SA was shown to be superior to diclofenac 3% gel in hyaluronic acid, as measured by the histological clearance of one defined lesion (72% vs. 59.1%) and by complete clinical clearance (55.4% vs. 32.0%). 5-FU-SA should be applied once daily to a total area of up to 25 cm(2), which may include the lesion(s) and a small area of surrounding skin (rim of healthy skin should not exceed 0.5 cm), for up to 12 weeks. The most common side effects are local inflammation and pruritus at the application site, and no serious adverse effects have been reported to date. Now commercially available in Canada, 5-FU-SA represents a patientapplied therapeutic option for the treatment of both overt and subclinical AKs.

Melanoma in-situ arising in seborrheic keratosis: a case report

PubMed Central

Repertinger, Susan; Wang, Jeff; Adickes, Edward; Sarma, Deba P

2008-01-01

Background Seborrheic keratosis is a very common benign skin tumor in man. Melanoma is rare but is the most dreaded of all malignant skin tumors. A melanoma arising in a seborrheic keratosis is distinctly rare. We are reporting such a case occurring in an 86-year-old man. Case presentation An-86-year-old male with a history of multiple actinic keratoses and seborrheic keratoses of the head and trunk presented with a mid-back skin lesion. The lesion was poorly circumscribed, flat, and gray, with a pink-tan, well-circumscribed scaly nodule within it. The biopsied lesion was composed of the usual features of hyperkeratotic seborrheic keratosis, but with focal atypical melanocytic proliferation with nesting along the dermal-epidermal junction. We interpreted this lesion as a melanoma in-situ arising within a seborrheic keratosis. Conclusion It is not uncommon for many physicians to remove a typical seborrheic keratosis without a confirmatory microscopic confirmation. We urge that all such lesions be examined by the pathologist to avoid missing another concomitant malignant lesion such as melanoma which needs adequate resection and close follow-up. PMID:18947402

Long-term (6 and 12 months) follow-up of two prospective, randomized, controlled phase III trials of photodynamic therapy with BF-200 ALA and methyl aminolaevulinate for the treatment of actinic keratosis.

PubMed

Dirschka, T; Radny, P; Dominicus, R; Mensing, H; Brüning, H; Jenne, L; Karl, L; Sebastian, M; Oster-Schmidt, C; Klövekorn, W; Reinhold, U; Tanner, M; Gröne, D; Deichmann, M; Simon, M; Hübinger, F; Hofbauer, G; Krähn-Senftleben, G; Borrosch, F; Reich, K; Berking, C; Wolf, P; Lehmann, P; Moers-Carpi, M; Hönigsmann, H; Wernicke-Panten, K; Hahn, S; Pabst, G; Voss, D; Foguet, M; Schmitz, B; Lübbert, H; Szeimies, R-M

2013-04-01

Two phase III trials of photodynamic therapy (PDT) with BF-200 ALA, a recently approved nanoemulsion formulation of 5-aminolaevulinic acid (ALA) demonstrated high clearance rates in mild-to-moderate actinic keratosis (AK). The comparison to a registered methyl aminolaevulinate (MAL) cream demonstrated significantly superior total patient clearance rates. To evaluate long-term efficacy and safety of PDT for AK 6 and 12 months after the last PDT with BF-200 ALA, MAL or placebo. The follow-up phase (FUP) was performed with patients of two phase III studies. Both studies compared BF-200 ALA with placebo, one of the studies additionally with MAL. Overall recurrence rates and various subgroups (light source, lesion severity, lesion location, complete responders after first PDT) were assessed 6 and 12 months after the last PDT. Recurrence rates were similar for BF-200 ALA and MAL, with a tendency to lower recurrence rates for BF-200 ALA. The proportion of patients who were fully cleared during PDT and remained completely clear for at least 12 months after PDT were 47% for BF-200 ALA (both studies) and 36% for MAL treatment. The subgroup that was illuminated with narrow wavelength LED lamps reached 69% and 53% for BF-200 ALA (both studies, respectively) and 41% for MAL. No safety concerns were reported. The FUP data confirmed the high efficacy and safety of PDT with BF-200 ALA. The slightly lower recurrence rates after BF-200 ALA treatment compared with MAL treatment enhanced the better treatment outcome due to the significantly superior efficacy. © 2012 Biofrontera Bioscience GmbH BJD © 2012 British Association of Dermatologists.

Dermatological Feasibility of Multimodal Facial Color Imaging Modality for Cross-Evaluation of Facial Actinic Keratosis

PubMed Central

Bae, Youngwoo; Son, Taeyoon; Nelson, J. Stuart; Kim, Jae-Hong; Choi, Eung Ho; Jung, Byungjo

2010-01-01

Background/Purpose Digital color image analysis is currently considered as a routine procedure in dermatology. In our previous study, a multimodal facial color imaging modality (MFCIM), which provides a conventional, parallel- and cross-polarization, and fluorescent color image, was introduced for objective evaluation of various facial skin lesions. This study introduces a commercial version of MFCIM, DermaVision-PRO, for routine clinical use in dermatology and demonstrates its dermatological feasibility for cross-evaluation of skin lesions. Methods/Results Sample images of subjects with actinic keratosis or non-melanoma skin cancers were obtained at four different imaging modes. Various image analysis methods were applied to cross-evaluate the skin lesion and, finally, extract valuable diagnostic information. DermaVision-PRO is potentially a useful tool as an objective macroscopic imaging modality for quick prescreening and cross-evaluation of facial skin lesions. Conclusion DermaVision-PRO may be utilized as a useful tool for cross-evaluation of widely distributed facial skin lesions and an efficient database management of patient information. PMID:20923462

A randomized comparative study of tolerance and satisfaction in the treatment of actinic keratosis of the face and scalp between 5% imiquimod cream and photodynamic therapy with methyl aminolaevulinate.

PubMed

Serra-Guillen, C; Nagore, E; Hueso, L; Llombart, B; Requena, C; Sanmartín, O; Botella-Estrada, R; Guillen, C

2011-02-01

Photodynamic therapy (PDT) and imiquimod are two excellent treatments for actinic keratosis but are often not well tolerated by patients. To ascertain which treatment is better tolerated and which produces greater patient satisfaction. A secondary objective was to determine the factors related to the patient's tolerance to each treatment. Patients with at least five actinic keratosis lesions on the face and scalp were selected. The patients were randomized to receive treatment with PDT with methyl aminolaevulinate or treatment with imiquimod. Tolerance, satisfaction and predisposition to repeat the treatment were evaluated. Most patients exhibited good or acceptable tolerance to both PDT and imiquimod treatment. There was a higher percentage of patients treated with PDT (93%) who were very satisfied compared with imiquimod (62%) (P=0·004). Most patients treated with either one of the two options would repeat the same treatment. No significant relationship was found between age, sex, working time exposed to the sun, phototype and hair colour and the tolerance to both treatments. Both PDT and imiquimod are treatments that are generally well tolerated. While both treatments provide a high level of satisfaction, PDT appears to be slightly superior in this regard. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

Comparison of 10 efficient protocols for photodynamic therapy of actinic keratosis: How relevant are effective light dose and local damage in predicting the complete response rate at 3 months?

PubMed

Vignion-Dewalle, Anne-Sophie; Baert, Gregory; Thecua, Elise; Lecomte, Fabienne; Vicentini, Claire; Abi-Rached, Henry; Mortier, Laurent; Mordon, Serge

2018-04-18

Topical photodynamic therapy is an established treatment modality for various dermatological conditions, including actinic keratosis. In Europe, the approved protocols for photodynamic therapy of actinic keratosis involve irradiation with either an Aktilite CL 128 lamp or daylight, whereas irradiation with the Blu-U illuminator is approved in the United States. Many other protocols using irradiation by a variety of light sources are also clinically efficient. This paper aims to compare 10 different protocols with clinically proven efficacy for photodynamic therapy of actinic keratosis and the available spectral irradiance of the light source. Effective irradiance, effective light dose, and local damage are compared. We also investigate whether there is an association between the complete response rate at 3 months and the effective light dose or local damage. The effective irradiance, also referred to as protoporphyrin IX-weighted irradiance, is obtained by integrating the spectral irradiance weighted by the normalized absorption spectrum of protoporphyrin IX over the wavelength. Integrating the effective irradiance over the irradiation time yields the effective light dose, which is also known as the protoporphyrin IX-weighted light dose. Local damage, defined as the total cumulative singlet oxygen molecules produced during treatment, is estimated using mathematical modeling of the photodynamic therapy process. This modeling is based on an iterative procedure taking into account the spatial and temporal variations in the protoporphyrin IX absorption spectrum during treatment. The protocol for daylight photodynamic therapy on a clear sunny day, the protocol for daylight photodynamic therapy on an overcast day, the photodynamic therapy protocol for a white LED lamp for operating rooms and the photodynamic therapy protocol for the Blu-U illuminator perform better than the six other protocols-all involving red light illumination-in terms of both effective light dose and

The challenge of diagnosing seborrheic keratosis by reflectance confocal microscopy.

PubMed

Guo, A; Chen, J; Yang, C; Ding, Y; Zeng, Q; Tan, L

2018-05-24

Seborrheic keratosis (SK) is one of the most common skin tumors seen by dermatologists. It should be differentiated with many diseases, especially skin tumors. Reflectance confocal microscopy (RCM) has been applied for evaluation of SK. There are a few studies that describe the RCM of SK. The aim of the study was to find the challenge of diagnosing seborrheic keratosis by reflectance confocal microscopy. A total of 390 patients with a clinical suspicious diagnosis of seborrheic keratosis were enrolled in this study, and lesions from each patient were imaged with RCM. Thirty-seven of these patients performed a biopsy in order to be given a histological diagnosis. We retrospectively analyzed the outcomes of RCM diagnosis and histological diagnosis, and then found the RCM characteristics of biopsy-proven lesions. According to RCM images, 258 of 390 (66.2%) patients were diagnosed with SK, 97 of 390 (24.9%) patients could not be diagnosed by the dermatologist according to RCM. Of all 37 biopsied lesions, 23 were SK, 6 were actinic keratosis, 2 were basal cell carcinoma, and 2 were squamous cell carcinoma. It is challenge to diagnose seborrheic keratosis by reflectance confocal microscopy. It may due to the variable clinical and RCM appearances of SK, and limited depth of RCM. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cost-Effectiveness and Cost-Utility Analysis of Ingenol Mebutate Versus Diclofenac 3% and Imiquimod 5% in the Treatment of Actinic Keratosis in Spain.

PubMed

Elías, I; Ortega-Joaquín, N; de la Cueva, P; Del Pozo, L J; Moreno-Ramírez, D; Boada, A; Aguilar, M; Mirada, A; Mosquera, E; Gibbons, C; Oyagüez, I

2016-01-01

To perform a cost-effectiveness and cost-utility analysis of ingenol mebutate in the treatment of actinic keratosis in Spain. We used an adapted Markov model to simulate outcomes in a cohort of patients (mean age, 73 years) with actinic keratosis over a 5-year period. The comparators were diclofenac 3% and imiquimod 5%. The analysis was performed from the perspective of the Spanish National Health System based on direct costs (2015 retail price plus value added tax less the mandatory discount). A panel of experts estimated resources, taking unit costs from national databases. An annual discount rate of 3% was applied. Deterministic and probabilistic sensitivity analyses were performed. The effectiveness of ingenol mebutate-with 0.192 and 0.129 more clearances gained in treatments for face and scalp lesions and trunk and extremity lesions, respectively-was superior to diclofenac's. The total costs of treatment with ingenol mebutate were lower at € 551.50 (face and scalp) and € 622.27 (trunk and extremities) than the respective costs with diclofenac (€ 849.11 and € 844.93). The incremental cost-effectiveness and cost-utility ratios showed that ingenol mebutate was a dominant strategy vs diclofenac. Ingenol mebutate also proved to be more effective than imiquimod, based on 0.535 and 0.503 additional clearances, and total costs of € 551.50 and € 527.89 for the two drugs, respectively. The resulting incremental cost-effectiveness ratio was € 728.64 per clearance gained with ingenol mebutate vs imiquimod. Ingenol mebutate was a dominant treatment option vs diclofenac and was efficient vs imiquimod (i.e., more effective at a higher cost, achieving an incremental cost-utility ratio of<€30000/quality-adjusted life-years). Copyright © 2016 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

Photodamage: all signs lead to actinic keratosis and early squamous cell carcinoma.

PubMed

Wei, Jerry; Kok, Lai Fong; Byrne, Scott N; Halliday, Gary M

2015-01-01

Ultraviolet (UV) radiation is likely to drive the initiation and progression of skin cancer from actinic keratosis to squamous cell carcinoma. Signs of photodamage occur at multiple steps. UV radiation damages many cellular constituents, including lipids, proteins and DNA, all of which are likely to contribute to UV-induced skin cancer. Two biological events culminating from photodamage are mutations in the genes critical to the control of cell division, differentiation and invasion and immunosuppression. DNA photodamage, if unrepaired prior to cell division, can result in the incorporation of an incorrect nucleotide into newly synthesised DNA. Mutations in critical genes contribute to carcinogenesis. Photodamage to proteins such as those involved in DNA repair or proteins or lipids involved in cellular signalling can interfere with this repair process and contribute to mutagenesis. Mutations in key genes, including TP53, BRM, PTCH1, and HRAS, contribute to skin carcinogenesis. UV also damages immunity. Photodamage to DNA and signalling lipids as well as other molecular changes are detrimental to the key cells that regulate immunity. Photodamaged dendritic cells and altered responses by mast cells lead to the activation of T and B regulatory cells that suppress immunity to the protein products of UV-mutated genes. This stops the immune response from its protective function of destroying mutated cells, enabling the transformed cells to progress to skin cancer. UV appears to play a pivotal role at each of these steps, and therefore, signs of photodamage point to the development of skin cancer. © 2015 S. Karger AG, Basel.

[Photodynamic therapy for actinic cheilitis].

PubMed

Castaño, E; Comunión, A; Arias, D; Miñano, R; Romero, A; Borbujo, J

2009-12-01

Actinic cheilitis is a subtype of actinic keratosis that mainly affects the lower lip and has a higher risk of malignant transformation. Its location on the labial mucosa influences the therapeutic approach. Vermilionectomy requires local or general anesthetic and is associated with a risk of an unsightly scar, and the treatment with 5-fluorouracil or imiquimod lasts for several weeks and the inflammatory reaction can be very intense. A number of authors have used photodynamic therapy as an alternative to the usual treatments. We present 3 patients with histologically confirmed actinic cheilitis treated using photodynamic therapy with methyl aminolevulinic acid as the photosensitizer and red light at 630 nm. The clinical response was good, with no recurrences after 3 to 6 months of follow-up. Our experience supports the use of photodynamic therapy as a good alternative for the treatment of actinic cheilitis.

A randomized trial comparing simultaneous vs. sequential field treatment of actinic keratosis with ingenol mebutate on two separate areas of the head and body.

PubMed

Pellacani, G; Peris, K; Guillen, C; Clonier, F; Larsson, T; Venkata, R; Puig, S

2015-11-01

Actinic keratoses (AKs) are precursors to invasive squamous cell carcinoma and can progress if untreated. Limited data support the use of ingenol mebutate to treat AKs on more than one area of the body simultaneously. To investigate safety, efficacy and treatment satisfaction when treating separate areas simultaneously or sequentially with different concentrations of ingenol mebutate gel. In this phase IIIb study (NCT01787383), patients with clinically visible, non-hyperkeratotic AKs on two separate treatment areas (face/scalp and trunk/extremities) were randomized to simultaneous or sequential treatment with ingenol mebutate gel (0.015% and 0.05%). Endpoints included composite local skin response (LSR) score 3 days after first application, complete AK clearance and percentage reduction in AKs at week 8. There were no statistically significant differences between simultaneous (n = 101) and sequential (n = 98) groups in composite LSR score (10.4 vs. 9.7), complete clearance (52.7% vs. 46.9%) or percentage reduction in AKs (83.4% vs. 79.1%). Mean composite LSR scores on face/scalp and trunk/extremities were similar for both groups. Adverse event (AE) incidence was comparable between groups, the most common treatment-related AEs being pruritus and pain at the application site. Treating AKs with ingenol mebutate simultaneously or sequentially gave similar results in terms of tolerability (LSR score, AEs) and efficacy (complete clearance). Therefore, the physician and patient can select the most convenient treatment regimen, with confidence in achieving a similar outcome. © 2015 LEO Pharma A/S. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons, Ltd. on behalf of European Academy of Dermatology and Venereology.

Topical treatment of actinic keratoses with low-dose 5-fluorouracil in combination with salicylic acid--pilot study.

PubMed

Schlaak, Max; Simon, Jan C

2010-03-01

Actinic keratoses (AK) are carcinomas in situ and can progress to invasive squamous cell carcinomas. Treatment of actinic keratoses can be achieved by physical ablation, chemotherapeutic agents, immunomodulators or photodynamic therapy. We conducted a proof of concept study with 15 patients. Overall 66 actinic keratoses were treated with 5-FU (0.5%) and salicylic acid (10%) for 4 weeks (3 times per week). After 12 weeks complete response of 47 AK (77%), partial response of 13 AK (21%) and non-response of 1 AK (2%) were achieved. Treatment was well tolerated and efficient.

Computational Study of the Binding Mechanism of Actin-Depolymerizing Factor 1 with Actin in Arabidopsis thaliana.

PubMed

Du, Juan; Wang, Xue; Dong, Chun-Hai; Yang, Jian Ming; Yao, Xiao Jun

2016-01-01

Actin is a highly conserved protein. It plays important roles in cellular function and exists either in the monomeric (G-actin) or polymeric form (F-actin). Members of the actin-depolymerizing factor (ADF)/cofilin protein family bind to both G-actin and F-actin and play vital roles in actin dynamics by manipulating the rates of filament polymerization and depolymerization. It has been reported that the S6D and R98A/K100A mutants of actin-depolymerizing factor 1 (ADF1) in Arabidopsis thaliana decreased the binding affinity of ADF for the actin monomer. To investigate the binding mechanism and dynamic behavior of the ADF1-actin complex, we constructed a homology model of the AtADF1-actin complex based on the crystal structure of AtADF1 and the twinfilin C-terminal ADF-H domain in a complex with a mouse actin monomer. The model was then refined for subsequent molecular dynamics simulations. Increased binding energy of the mutated system was observed using the Molecular Mechanics Generalized Born Surface Area and Poisson-Boltzmann Surface Area (MM-GB/PBSA) methods. To determine the residues that make decisive contributions to the ADF1 actin-binding affinity, per-residue decomposition and computational alanine scanning analyses were performed, which provided more detailed information on the binding mechanism. Root-mean-square fluctuation and principal component analyses confirmed that the S6D and R98A/K100A mutants induced an increased conformational flexibility. The comprehensive molecular insight gained from this study is of great importance for understanding the binding mechanism of ADF1 and G-actin.

Computational Study of the Binding Mechanism of Actin-Depolymerizing Factor 1 with Actin in Arabidopsis thaliana

PubMed Central

Wang, Xue; Dong, Chun-Hai; Yang, Jian Ming; Yao, Xiao Jun

2016-01-01

Actin is a highly conserved protein. It plays important roles in cellular function and exists either in the monomeric (G-actin) or polymeric form (F-actin). Members of the actin-depolymerizing factor (ADF)/cofilin protein family bind to both G-actin and F-actin and play vital roles in actin dynamics by manipulating the rates of filament polymerization and depolymerization. It has been reported that the S6D and R98A/K100A mutants of actin-depolymerizing factor 1 (ADF1) in Arabidopsis thaliana decreased the binding affinity of ADF for the actin monomer. To investigate the binding mechanism and dynamic behavior of the ADF1–actin complex, we constructed a homology model of the AtADF1–actin complex based on the crystal structure of AtADF1 and the twinfilin C-terminal ADF-H domain in a complex with a mouse actin monomer. The model was then refined for subsequent molecular dynamics simulations. Increased binding energy of the mutated system was observed using the Molecular Mechanics Generalized Born Surface Area and Poisson–Boltzmann Surface Area (MM-GB/PBSA) methods. To determine the residues that make decisive contributions to the ADF1 actin-binding affinity, per-residue decomposition and computational alanine scanning analyses were performed, which provided more detailed information on the binding mechanism. Root-mean-square fluctuation and principal component analyses confirmed that the S6D and R98A/K100A mutants induced an increased conformational flexibility. The comprehensive molecular insight gained from this study is of great importance for understanding the binding mechanism of ADF1 and G-actin. PMID:27414648

Non-ablative fractional resurfacing in combination with topical tretinoin cream as a field treatment modality for multiple actinic keratosis: a pilot study and a review of other field treatment modalities.

PubMed

Prens, Sebastiaan P; de Vries, Karin; Neumann, H A Martino; Prens, Errol P

2013-06-01

Actinic keratoses (AK) are premalignant lesions occurring mainly in sun-damaged skin. Current topical treatment options for AK and photo-damaged skin such as liquid nitrogen and electrosurgery are not suitable for field treatment. Otherwise, therapies suitable for field treatment bring along considerable patient discomfort. Non-ablative fractional resurfacing has emerged as a logical treatment option especially for field treatment of AK. To evaluate the clinical efficacy of fractional laser therapy for clearing AK and improving skin quality. To compare patient friendliness of the "fractional" therapy with those reported for other field treatment modalities. Ten patients with Fitzpatrick skin type I to III with multiple AK and extensive sun-damaged skin, received 5-10 sessions with a 4-week interval using a 1550 nm Erbium-Glass Fractionated laser (Sellas, Korea). Four weeks and 24 weeks after the last treatment the clinical results were evaluated by an independent physician. The mean degree of improvement, in terms of reduction in the number of AK and improvement of skin texture, was 54% on a 4 point PGA scale, and persisted for approximately 6 months. The biggest advantage of fractional laser treatment, besides the eradication of AK and a clear rejuvenation effect, is the absence of "downtime". Fractional non-ablative resurfacing induces significant reduction in the number of AK and improves the skin quality. Also all patients preferred fractional laser therapy above other AK treatment modalities.

[Retrospective, descriptive, observational study of treatment of multiple actinic keratoses with topical methyl aminolevulinate and red light: results in clinical practice and correlation with fluorescence imaging].

PubMed

Fernández-Guarino, M; Harto, A; Sánchez-Ronco, M; Pérez-García, B; Marquet, A; Jaén, P

2008-12-01

Actinic keratosis (AK) is one of the most common skin diseases seen in clinical practice. In the last 5 years, several studies assessing the efficacy of photodynamic therapy in the treatment of multiple AKs have been published. We aimed to assess the clinical outcomes of photodynamic therapy in patients with multiple AKs and the correlation of those outcomes with fluorescence imaging. In this retrospective, descriptive, observational study of 57 patients treated in our hospital with photodynamic therapy for multiple AKs, we recorded age, sex, and lesion site (face, scalp, and dorsum of the hands). All patients were treated in the same way: methyl aminolevulinic acid (Metvix) was applied for 3 hours and the skin then irradiated with red light at 630 nm, 37 J/cm(2), for 7.5 minutes (Aktilite). The response, remission duration, tolerance, number of sessions, and fluorescence images were recorded by site. The chi(2) test was used to assess between-site differences and the correlation between fluorescence imaging and clinical response. The greatest improvements were obtained for facial lesions; these required fewer sessions and remission lasted longer than lesions at other sites. The treatment was best tolerated on the dorsum of the hands. The fluorescence area and the reduction in intensity on applying treatment were found to be strongly and significantly correlated with the extent of clinical response. Overall, the outcomes of treatment of multiple AKs with photodynamic therapy are better for the face than for the scalp and dorsum of the hands. Fluorescence imaging may be an effective tool for predicting response to treatment.

Expression of lumican in hidroacanthoma simplex and clonal-type seborrheic keratosis as a potent differential diagnostic marker.

PubMed

Takayama, Ryoko; Ansai, Shin-Ichi; Ishiwata, Toshiyuki; Yamamoto, Tetsushi; Matsuda, Yoko; Naito, Zenya; Kawana, Seiji

2014-08-01

Lumican, a member of the small leucine-rich proteoglycan family, regulates the assembly and diameter of collagen fibers in the extracellular matrix of various tissues. The lumican expression correlates with pathological conditions and the growth and metastasis of various malignancies. In cutaneous neoplasms, the lumican expression is lower in advanced-stage malignant melanomas that invade the dermis than in early-stage melanomas. Furthermore, we have recently reported that the expression pattern of lumican is different from that of actinic keratosis and the Bowen disease. Lumican is positive in the poroid cells of intraepidermal sweat ducts; therefore, we examined the expression patterns of lumican in acanthotic-type seborrheic keratosis and Pinkus-type poroma followed by clonal-type seborrheic keratosis and hidroacanthoma simplex. The neoplastic cells of acanthotic-type seborrheic keratosis exhibited positive immunostaining in only 1 of 31 cases (3.23%), whereas the poroid cells of Pinkus-type poroma exhibited positive immunoreactivity in 26 of 28 patients (92.8%). In the hidroacanthoma simplex cases, lumican was expressed in poroid cells forming intraepidermal nests in 22 of 28 patients (78.6%), whereas the neoplastic cells in most cases of clonal-type seborrheic keratosis were negative for lumican. In some seborrheic keratosis cases that were positive for lumican in neoplastic cells, lumican was observed in squamoid cells but not in basaloid cells. Therefore, it is necessary to evaluate the immunoreactivity of lumican in seborrheic keratosis and in basaloid cells. These findings suggest that lumican is a potent differential diagnostic marker that distinguishes hidroacanthoma simplex from clonal-type seborrheic keratosis.

Ingenol mebutate gel treatment for actinic cheilitis: report of four cases.

PubMed

Barrado Solís, Nerea; Molés Poveda, Paula; Lloret Ruiz, César; Pont Sanjuan, Virginia; Velasco Pastor, Manel; Quecedo Estébanez, Esther; Miquel Miquel, Javier

2015-01-01

Actinic cheilitis (AC) are premalignant lesions that have an increased risk of malignant transformation. Their treatment, therefore, is essential to prevent carcinogenesis. However, optimal therapy is not well established and different modalities yield variable results. Ingenol mebutate gel has recently been approved by the US Food and Drug Administration for topical treatment of actinic keratosis, with high clearance rates. On the basis of these findings, we report our experience with this drug for the treatment of AC. © 2014 Wiley Periodicals, Inc.

Red light photodynamic therapy for actinic keratosis using 37 J/cm2 : Fractionated irradiation with 12.3 mW/cm2 after 30 minutes incubation time compared to standard continuous irradiation with 75 mW/cm2 after 3 hours incubation time using a mathematical modeling.

PubMed

Vignion-Dewalle, Anne-Sophie; Baert, Gregory; Devos, Laura; Thecua, Elise; Vicentini, Claire; Mortier, Laurent; Mordon, Serge

2017-09-01

Photodynamic therapy (PDT) is an emerging treatment modality for various diseases, especially for dermatological conditions. Although, the standard PDT protocol for the treatment of actinic keratoses in Europe has shown to be effective, treatment-associated pain is often observed in patients. Different modifications to this protocol attempted to decrease pain have been investigated. The decrease in fluence rate seems to be a promising solution. Moreover, it has been suggested that light fractionation significantly increases the efficacy of PDT. Based on a flexible light-emitting textile, the FLEXITHERALIGHT device specifically provides a fractionated illumination at a fluence rate more than six times lower than that of the standard protocol. In a recently completed clinical trial of PDT for the treatment of actinic keratosis, the non-inferiority of a protocol involving illumination with the FLEXITHERALIGHT device after a short incubation time and referred to as the FLEXITHERALIGHT protocol has been assessed compared to the standard protocol. In this paper, we propose a comparison of the two above mentioned 635 nm red light protocols with 37 J/cm 2 in the PDT treatment of actinic keratosis: the standard protocol and the FLEXITHERALIGHT one through a mathematical modeling. This mathematical modeling, which slightly differs from the one we have already published, enables the local damage induced by the therapy to be estimated. The comparison performed in terms of the local damage induced by the therapy demonstrates that the FLEXITHERALIGHT protocol with lower fluence rate, light fractionation and shorter incubation time is somewhat less efficient than the standard protocol. Nevertheless, from the clinical trial results, the FLEXITHERALIGHT protocol results in non-inferior response rates compared to the standard protocol. This finding raises the question of whether the PDT local damage achieved by the FLEXITHERALIGHT protocol (respectively, the standard protocol

Effective photodynamic therapy of actinic keratoses on the head and face with a novel, self-adhesive 5-aminolaevulinic acid patch.

PubMed

Hauschild, Axel; Popp, Georg; Stockfleth, Eggert; Meyer, Karl-Gustav; Imberger, Dirk; Mohr, Peter; Itschert, Götz; Kaufmann, Roland; Neuber, Karsten; Frambach, Yvonne; Gollnick, Harald; Brunnert, Marcus; Stocker, Marcus; Ortland, Christoph; Karrer, Sigrid

2009-02-01

Photodynamic therapy (PDT) is increasingly used for the treatment of actinic keratosis (AK). To investigate both the efficacy of different application times and the safety of a novel patch (PD P 506 A) containing aminolaevulinic acid in the PDT of mild to moderate AK. Applications of PD P 506 A for 0.5, 1, 2 and 4 h were compared in a multicentre, randomized, blinded-observer, parallel-group study. After patch removal, study lesions were illuminated with red light (lambda(em) approximately 630 nm; 37 J/cm(2)). Study lesions were not pretreated (e.g. by curettage) prior to PDT. Efficacy was evaluated 4 and 8 weeks after treatment. Safety and tolerability were determined through laboratory analyses and documentation of both local reactions and adverse events. A total of 149 patients were initially enrolled. Of these, 140 patients (520 lesions) completed the study according to protocol. Eight weeks after treatment, 86% of the AK lesions (74% of the patients) treated with 4-h patch application showed complete clearance. The complete clearance rates of lesions (patients) for the 2-, 1- and 0.5-h treatment arms were 73% (47%), 72% (50%) and 51% (24%), respectively. Statistically, the 4-h application was identified as the 'best treatment'. Patients with clearance seemed to experience local reactions to a greater extent than patients without clearance. Local reactions to study treatments did not exceed the expected range. The results of this first clinical efficacy study suggest excellent therapeutic outcomes with a single PD P 506 A PDT with a 4-h application.

Dysplastic nevus associated with seborrheic keratosis*

PubMed Central

Botelho, Luciane Francisca Fernandes; Michalany, Nilceo Schwery; Enokihara, Milvia Maria Simões e Silva; Hirata, Sergio Henrique

2014-01-01

Seborrheic keratosis is a common skin lesion which may coincidentally be associated melanocytic nevi. The authors describe a case of dysplastic nevus associated with seborrheic keratosis and discuss the clinical, dermoscopic, and histological findings of this association. They also discuss the association between seborrheic keratosis and other benign and malignant tumours. PMID:24626665

Consensus recommendations on the use of daylight photodynamic therapy with methyl aminolevulinate cream for actinic keratoses in Australia

PubMed Central

Shumack, Stephen; Murrell, Dedee F; Rubel, Diana M; Fernández‐Peñas, Pablo; Salmon, Robert; Hewitt, Daniel; Foley, Peter; Spelman, Lynda

2015-01-01

Abstract Australia has the highest prevalence of actinic keratoses (AK) worldwide. Because of the risk of transformation of AK to invasive squamous cell carcinomas, consensus guidelines recommend that AK are removed using appropriate therapies to prevent progression to invasive disease. Daylight photodynamic therapy (PDT) is emerging as an efficacious treatment for AK, particularly for patients who require treatment of large areas of chronic actinic damage that can be exposed easily to daylight. Daylight PDT with methyl aminolevulinate (MAL) cream is a simple treatment for AK, almost painless, well tolerated and convenient, requiring minimal time in the clinic. Randomised controlled studies from northern Europe and Australia support the use of daylight PDT as an effective therapy for grade I and II AK on the face and scalp. There is sufficient daylight to conduct daylight PDT in Australia at any time of the year and during most weather conditions. Hence, daylight PDT with MAL can be included as an effective and well‐tolerated new treatment option for the treatment of AK in Australia. These consensus recommendations provide guidelines for Australian clinicians on the use of daylight PDT in the treatment of diagnosed AK. PMID:26033230

Dual-channel red/blue fluorescence dosimetry with broadband reflectance spectroscopic correction measures protoporphyrin IX production during photodynamic therapy of actinic keratosis

NASA Astrophysics Data System (ADS)

Kanick, Stephen Chad; Davis, Scott C.; Zhao, Yan; Hasan, Tayyaba; Maytin, Edward V.; Pogue, Brian W.; Chapman, M. Shane

2014-07-01

Dosimetry for aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy of actinic keratosis was examined with an optimized fluorescence dosimeter to measure PpIX during treatment. While insufficient PpIX generation may be an indicator of incomplete response, there exists no standardized method to quantitate PpIX production at depths in the skin during clinical treatments. In this study, a spectrometer-based point probe dosimeter system was used to sample PpIX fluorescence from superficial (blue wavelength excitation) and deeper (red wavelength excitation) tissue layers. Broadband white light spectroscopy (WLS) was used to monitor aspects of vascular physiology and inform a correction of fluorescence for the background optical properties. Measurements in tissue phantoms showed accurate recovery of blood volume fraction and reduced scattering coefficient from WLS, and a linear response of PpIX fluorescence versus concentration down to 1.95 and 250 nM for blue and red excitations, respectively. A pilot clinical study of 19 patients receiving 1-h ALA incubation before treatment showed high intrinsic variance in PpIX fluorescence with a standard deviation/mean ratio of >0.9. PpIX fluorescence was significantly higher in patients reporting higher pain levels on a visual analog scale. These pilot data suggest that patient-specific PpIX quantitation may predict outcome response.

Keratosis pilaris on the cheek (image)

MedlinePlus

Keratosis pilaris occurs most commonly during childhood and produces small, rough spots. called papules, that are typically ... especially during winter months, makes the condition worse. Keratosis pilaris tends to be inherited and may be ...

Dual-channel red/blue fluorescence dosimetry with broadband reflectance spectroscopic correction measures protoporphyrin IX production during photodynamic therapy of actinic keratosis

PubMed Central

Kanick, Stephen Chad; Davis, Scott C.; Zhao, Yan; Hasan, Tayyaba; Maytin, Edward V.; Pogue, Brian W.; Chapman, M. Shane

2014-01-01

Abstract. Dosimetry for aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy of actinic keratosis was examined with an optimized fluorescence dosimeter to measure PpIX during treatment. While insufficient PpIX generation may be an indicator of incomplete response, there exists no standardized method to quantitate PpIX production at depths in the skin during clinical treatments. In this study, a spectrometer-based point probe dosimeter system was used to sample PpIX fluorescence from superficial (blue wavelength excitation) and deeper (red wavelength excitation) tissue layers. Broadband white light spectroscopy (WLS) was used to monitor aspects of vascular physiology and inform a correction of fluorescence for the background optical properties. Measurements in tissue phantoms showed accurate recovery of blood volume fraction and reduced scattering coefficient from WLS, and a linear response of PpIX fluorescence versus concentration down to 1.95 and 250 nM for blue and red excitations, respectively. A pilot clinical study of 19 patients receiving 1-h ALA incubation before treatment showed high intrinsic variance in PpIX fluorescence with a standard deviation/mean ratio of >0.9. PpIX fluorescence was significantly higher in patients reporting higher pain levels on a visual analog scale. These pilot data suggest that patient-specific PpIX quantitation may predict outcome response. PMID:24996661

Seborrheic Keratosis of the Conjunctiva: A Case Report

PubMed Central

Kim, Ji Hyun; Bae, Hyoung Won; Lee, Kwang Kil; Kim, Tae Im

2009-01-01

Seborrheic keratosis is a benign epithelial neoplasia that occurs mainly in the skin of the eyelids and face. We describe a case of seborrheic keratosis of the conjunctiva confirmed by histopathology. A 72-year-old man presented with a recurrent conjunctival mass involving the nasal side of his right eye. Clinically, a diagnosis of conjunctival papilloma was made, and a mass excision was performed. The histopathological analysis evidenced a conjunctival-covering epithelium with papillomatous changes and irregular acanthosis, at the expense of a proliferation of basaloid cells. In addition, the lesion exhibited multiple pseudohorn cysts containing keratin. With the above findings, a diagnosis of conjunctival seborrheic keratosis was established. The occurrence of seborrheic keratosis on the conjunctiva is rare. In this case, seborrheic keratosis was confirmed by pathologic report despite its similar appearance with papilloma. Seborrheic keratosis should be considered in the differential diagnosis of conjunctival lesions. PMID:20046694

Breastfeeding keratosis: this frictional keratosis of newborns may mimic thrush.

PubMed

Kiat-Amnuay, Sudarat; Bouquot, Jerry

2013-09-01

We report the first example, to our knowledge, of a frictional keratosis from exuberant sucking in a breastfeeding infant. A 2-month-old girl was referred for evaluation of a well-demarcated, nonsloughing white keratotic plaque of the lower lip mucosa, just inside the vermilion border. The plaque had a slightly irregular surface, had no surrounding erythema, and was the only such plaque in the mouth. It had been present for at least 3 weeks and had been unsuccessfully treated by her pediatrician via oral Mycostatin (nystatin). Her parents sought a second opinion when the infant was prescribed a full course of oral Diflucan (fluconazole). A cytopathology smear (Papanicolaou test) revealed abundant mature keratinocytes with no evidence of Candida. The mother admitted that the infant "worked hard" at sucking during breastfeeding and continued sucking long after feeding. The parents were unaware of any other habit or potential irritation of the lips. After 3 months of age the infant's sucking pattern became more "normal" and the keratosis disappeared; it did not recur during 3 years of follow-up. We propose the term "breastfeeding keratosis" for this entity.

Switching From Conventional Photodynamic Therapy to Daylight Photodynamic Therapy For Actinic Keratoses: Systematic Review and Meta-analysis.

PubMed

Tomás-Velázquez, A; Redondo, P

2017-05-01

Actinic keratosis is a precursor lesion to the most common nonmelanoma skin cancer. Conventional photodynamic therapy (PDT) has been shown to be effective, but the procedure is time-consuming, can be very painful, and requires infrastructure. These shortcomings led to the emergence of daylight PDT. To obtain a global estimate of efficacy, we undertook a systematic literature review and performed a meta-analysis of the available evidence on the efficacy and safety of daylight PDT as compared to conventional PDT in the treatment of actinic keratosis and/or field cancerization. The conclusion is that the difference in efficacy is clinically negligible (global estimate of the mean response rate difference, -3.69%; 95% CI, -6.54% to -0.84%). The adverse effects of daylight PDT are mild and localized (79% of patients report no discomfort), and patients report less pain (P<.001). Daylight PDT gives good to excellent cosmetic results in more than 90% of patients, and patient satisfaction is greater (P<.001). Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Psoriasiform keratosis - case report.

PubMed

Pires, Carla Andréa Avelar; Sousa, Brena Andrade de; Nascimento, Carla do Socorro Silva do; Moutinho, Ana Thais Machado; Miranda, Mario Fernando Ribeiro de; Carneiro, Francisca Regina Oliveira

2014-01-01

Psoriasiform Keratosis is a rare clinic entity. The etiopathogenesis remains unknown and the disease is characterized by a solitary, scaly or keratotic papule, or plaque mainly located on the extremities. Histopathological features closely resemble those of psoriasis. We report the case of a 70-year-old woman presenting a solitary and asymptomatic keratotic plaque, located on the back of the left leg, unresponsive to topical corticosteroids. We performed an excisional biopsy and histopathology was consistent with psoriasiform keratosis.

Psoriasiform Keratosis - Case report*

PubMed Central

Pires, Carla Andréa Avelar; de Sousa, Brena Andrade; do Nascimento, Carla do Socorro Silva; Moutinho, Ana Thais Machado; de Miranda, Mario Fernando Ribeiro; Carneiro, Francisca Regina Oliveira

2014-01-01

Psoriasiform Keratosis is a rare clinic entity. The etiopathogenesis remains unknown and the disease is characterized by a solitary, scaly or keratotic papule, or plaque mainly located on the extremities. Histopathological features closely resemble those of psoriasis. We report the case of a 70-year-old woman presenting a solitary and asymptomatic keratotic plaque, located on the back of the left leg, unresponsive to topical corticosteroids. We performed an excisional biopsy and histopathology was consistent with psoriasiform keratosis. PMID:24770510

Online consensus conferences for clinical guidelines development - a survey among participants from the International Guidelines for the Treatment of Actinic Keratosis.

PubMed

Werner, Ricardo N; Jacobs, Anja; Rosumeck, Stefanie; Nast, Alexander

2014-12-01

Guideline development requires considerable time and financial resources. New technical devices such as software for online conferences may help to reduce time and financial efforts of guidelines development. The present survey may serve as an explorative pilot for a future study to determine the technical feasibility, acceptability and possible weaknesses of online consensus conferences for clinical guidelines development. An anonymous online survey was conducted among participants in the online consensus conference of the International League of Dermatological Societies (ILDS) Guidelines for the Treatment of Actinic Keratosis. The majority of participants reported no technical problems with the participation in the online consensus conference; one participant had substantial technical problems accountable to a regional telephone breakdown. The majority of participants would not have preferred a traditional face-to-face conference, and all participants rated online consensus conferences for international guidelines as absolutely acceptable. Rates of acceptance were particularly high among those participants with prior experience with consensus conferences. Certain aspects, particularly the possibilities of debating, were rated as possibly superior in face-to-face conferences by some participants. The data from the online survey indicate that online consensus conferences may be an appropriate alternative to traditional face-to-face consensus conferences, especially within the frame of international guidelines that would require high travel costs and time. Further research is necessary to confirm the data from this explorative pilot study. © 2014 John Wiley & Sons, Ltd.

Using Optical Coherence Tomography to Evaluate Skin Sun Damage and Precancer

PubMed Central

Korde, Vrushali R.; Bonnema, Garret T.; Xu, Wei; Krishnamurthy, Chetankumar; Ranger-Moore, James; Saboda, Kathylynn; Slayton, Lisa D.; Salasche, Stuart J.; Warneke, James A.; Alberts, David S.; Barton, Jennifer K.

2008-01-01

Background and Objectives Optical coherence tomography (OCT) is a depth resolved imaging modality that may aid in identifying sun damaged skin and the precancerous condition actinic keratosis (AK). Study Design/Materials and Methods OCT images were acquired of 112 patients at 2 sun protected and 2 sun exposed sites, with a subsequent biopsy. Each site received a dermatological evaluation, a histological diagnosis, and a solar elastosis (SE) score. OCT images were examined visually and statistically analyzed. Results Characteristic OCT image features were identified of sun protected, undiseased, sun damaged, and AK skin. A statistically significant difference (P < 0.0001) between the average attenuation values of skin with minimal and severe solar elastosis was observed. Significant differences (P < 0.0001) were also found between undiseased skin and AK using a gradient analysis. Using image features, AK could be distinguished from undiseased skin with 86% sensitivity and 83% specificity. Conclusion OCT has the potential to guide biopsies and provide non-invasive measures of skin sun damage and disease state, possibly increasing efficiency of chemopreventive agent trials. PMID:17960754

Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates

PubMed Central

Chitsazzadeh, Vida; Coarfa, Cristian; Drummond, Jennifer A.; Nguyen, Tri; Joseph, Aaron; Chilukuri, Suneel; Charpiot, Elizabeth; Adelmann, Charles H.; Ching, Grace; Nguyen, Tran N.; Nicholas, Courtney; Thomas, Valencia D.; Migden, Michael; MacFarlane, Deborah; Thompson, Erika; Shen, Jianjun; Takata, Yoko; McNiece, Kayla; Polansky, Maxim A.; Abbas, Hussein A.; Rajapakshe, Kimal; Gower, Adam; Spira, Avrum; Covington, Kyle R.; Xiao, Weimin; Gunaratne, Preethi; Pickering, Curtis; Frederick, Mitchell; Myers, Jeffrey N.; Shen, Li; Yao, Hui; Su, Xiaoping; Rapini, Ronald P.; Wheeler, David A.; Hawk, Ernest T.; Flores, Elsa R.; Tsai, Kenneth Y.

2016-01-01

Cutaneous squamous cell carcinoma (cuSCC) comprises 15–20% of all skin cancers, accounting for over 700,000 cases in USA annually. Most cuSCC arise in association with a distinct precancerous lesion, the actinic keratosis (AK). To identify potential targets for molecularly targeted chemoprevention, here we perform integrated cross-species genomic analysis of cuSCC development through the preneoplastic AK stage using matched human samples and a solar ultraviolet radiation-driven Hairless mouse model. We identify the major transcriptional drivers of this progression sequence, showing that the key genomic changes in cuSCC development occur in the normal skin to AK transition. Our data validate the use of this ultraviolet radiation-driven mouse cuSCC model for cross-species analysis and demonstrate that cuSCC bears deep molecular similarities to multiple carcinogen-driven SCCs from diverse sites, suggesting that cuSCC may serve as an effective, accessible model for multiple SCC types and that common treatment and prevention strategies may be feasible. PMID:27574101

Intraepidermal proliferation of Merkel cells within a seborrheic keratosis: Merkel cell carcinoma in situ or Merkel cell hyperplasia?

PubMed

McFalls, Jeanne; Okon, Lauren; Cannon, Sarah; Lee, Jason B

2017-05-01

Intradepidermal proliferation of Merkel cells without any dermal component has been interpreted as either a hyperplastic process secondary to chronic ultraviolet radiation or a neoplastic process, namely Merkel cell carcinoma (MCC) in situ. The recent criteria that have been proffered to diagnose MCC in situ, unfortunately, are identical to those that have been applied to Merkel cell hyperplasia in the past, posing a diagnostic quandary when faced with an intraepidermal proliferation of Merkel cells. Most previously reported cases of MCC in situ have occurred within associated epithelial lesion that includes solar (actinic) keratosis and squamous-cell carcinoma in situ. Similarly, Merkel cell hyperplasia has been reported to occur in association with a variety of epithelial lesions as well as on chronically sun-damaged skin. Herein, a case of an intraepidermal proliferation of Merkel cells within a seborrheic keratosis is presented accompanied by a discussion on whether the proliferation represents another case of Merkel cell carcinoma in situ or an incidental hyperplastic process on chronically sun-damaged skin. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

GIANT PEDUNCULATED SEBORRHEIC KERATOSIS OF PENIS

PubMed Central

Thakur, Jagdeep S; Thakur, Anamika; Chauhan, C G S; Diwana, Vijay K; Chauhan, D C

2008-01-01

Seborrheic keratosis of the penis is a rare entity. It has been mistaken as genital warts and differentiation is only made on histopathology. We are reporting a case presenting as multiple giant polypoidal lesions on the penile skin for the last 20 years. Seborrheic keratosis should be considered in the differential diagnosis of pedunculated lesions of the penis. The histopathology after shave excision will be diagnostic. PMID:19967020

A case of keratosis lichenoid chronica.

PubMed

Baczewski, Natasha; Albano, Brian

2012-01-01

Keratosis lichenoid chronica is a rare dermatologic anomaly believed to be a variant of lichen planus. It presents as violaceous, nodular lesions usually on the dorsal aspects of the extremities and the trunk. The disease is refractory to treatment although psoralen ultraviolet A therapy and oral retinoids have been proven useful in some cases. Here we present the case of a 58-year-old male diagnosed with keratosis lichenoid chronica.

Cryotherapy - skin

MedlinePlus

... skin; Warts - freezing; Warts - cryotherapy; Actinic keratosis - cryotherapy; Solar keratosis - cryotherapy ... warts Destroy precancerous skin lesions (actinic keratoses or solar keratoses) In rare cases, cryotherapy is used to ...

A case of new onset keratosis pilaris after discontinuation of erlotinib.

PubMed

Okereke, Uchenna R; Colozza, Sara; Cohen, David E

2014-11-01

Keratosis pilaris and keratosis pilaris-like eruptions have been reported in association with RAF inhibitors sorafenib and vemurafenib. We describe herein what is to our knowledge the first reported case of new onset keratosis pilaris after discontinuation of EGFR inhibitor erlotinib. A 60 year-old female with stage IV lung cancer was treated with erlotinib (100 mg/d). The patient elected to discontinue erlotinib after four years secondary to adverse systemic reactions. However, five months later small, monomorphic, rough, folliculocentric papules with surrounding mild erythema characteristic of keratosis pilaris were noted on upper back and arms. This serves as the first documented case of new onset keratosis pilaris in a patient after discontinuation of erlotinib. We report the present case to show the possible association of keratosis pilaris with not only RAF inhibitors, but also the EGFR inhibitor erlotinib. Further investigation will determine whether this is a class effect with other systemic EGFR inhibitors.

Two cases of seborrheic keratosis with basal clear cells.

PubMed

Anan, Takashi; Fukumoto, Takaya; Kimura, Tetsunori

2017-03-01

Seborrheic keratosis with basal clear cells (SKBCC) is an extremely rare histopathological variant of seborrheic keratosis that has histological similarities to melanoma in situ. We herein report two cases of SKBCC and provide the first description of the dermoscopic features of this condition, in addition to the histopathological findings. Both of the two lesions showed typical histological architectures of seborrheic keratosis with rows or focal clusters of monomorphic clear cells with abundant pale cytoplasm and small round nucleus in the basal layer. Immunohistochemical examination revealed that most clear cells were positive for high molecular weight cytokeratin (34βE12) in a peripheral pattern but were negative tor Melan-A. Dermoscopy revealed typical features of ordinary seborrheic keratosis, while unfortunately did not reflect the presence of basal clear cells. © 2016 Japanese Dermatological Association.

Keratosis follicularis spinulosa decalvans and acne keloidalis nuchae.

PubMed

Goh, Michelle S Y; Magee, Jill; Chong, Alvin H

2005-11-01

A 27-year-old man presented with a 10-year history of scarring alopecia on the vertex of the scalp associated with follicular crusting and pustule formation, and a papular eruption on the posterior neck. Additionally, there was keratosis pilaris on the cheeks, eyebrows and thighs. Histology from the vertex showed scarring with a mixed perifollicular inflammatory infiltrate and foci of acute suppurative folliculitis. With clinical correlation, the diagnosis of keratosis follicularis spinulosa decalvans and concurrent acne keloidalis nuchae was made. The association of keratosis follicularis spinulosa decalvans with acne keloidalis nuchae has not previously been described. The patient responded to treatment with oral isotretinoin 20 mg (0.25 mg/kg) daily for 12 months.

Quality of life in the actinic neoplasia syndrome: The VA Topical Tretinoin Chemoprevention (VATTC) Trial

PubMed Central

Weinstock, Martin A.; Lee, Kachiu C.; Chren, Mary-Margaret; Marcolivio, Kimberly

2013-01-01

Background Keratinocyte carcinomas (KCs) are the most common malignancies of the skin. As lesions have a low mortality rate, understanding quality-of-life (QoL) factors is necessary in their management. Objective To assess QoL and associated patient characteristics in those with a history of keratinocyte carcinomas. Methods We conducted a cross-sectional study of veterans with a history of KCs enrolled in a randomized controlled trial for chemoprevention of keratinocyte carcinomas. Study dermatologists counted actinic keratoses (AKs) and assessed for skin photodamage. QoL was assessed using Skindex-29 and KC-specific questions. Demographics were self-reported. Results Participants (n = 931) enrolled at 5 clinical sites had worse QoL on all subscales (emotions, functioning, and symptoms) compared to a reference group of patients without skin disease. Univariate analysis demonstrated worse QoL associated with higher AK count, past 5-fluorouracil (5-FU) use, and greater sun sensitivity. Multivariate analysis demonstrated that higher AK count and past 5-FU use were independently related to diminished QoL. Higher comorbidities showed modest associations on the symptoms and functioning subscales. Number of previous KCs was not independently associated with any QoL differences. Limitations Study population may not be generalizable to the general population. Counting of AKs is of limited reliability. Previous 5-FU use is self reported. Conclusions A history of ever use of 5-FU and present AKs was strongly associated with worse QoL. We find it more useful to consider these patients as having the chronic condition “actinic neoplasia syndrome,” whose burden may be best measured by factors other than their history of KCs. PMID:19398145

Actinic keratosis

MedlinePlus

... near surfaces that reflect light, such as water, sand, concrete, and areas painted white. Sunlight is more ... A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among ...

Bowenoid transformation in seborrheic keratosis: A retrospective analysis of 429 patients

PubMed Central

Rajabi, Parvin; Adibi, Neda; Nematollahi, Pardis; Heidarpour, Mitra; Eftekhari, Mehdi; Siadat, Amir Hossein

2012-01-01

Background: Seborrheic keratosis is a common, benign skin tumor. Numerous reports have shown its possibility of malignant transformation. This study was designed to demonstrate the occurrence of concomitant seborrheic keratosis and skin cancers. Materials and Methods: Data was retrospectively reviewed from all patients with a diagnosis of seborrheic keratosis in pathology department of Alzahra Hospital and a private pathology laboratory in Isfahan, Iran over a 4-year period. We classified all demographic data and associated dysplasia or Bowen's disease and analyzed them by student-t or chi-square tests. Results: From all 429 specimens, 5 (1.2%) were found to be associated with Bowen's disease and one (0.2%) with mild dysplasia in squamous epithelium. All cases arose within the clinically, atypical seborrheic keratosis. More men were affected with lesions alone and with malignancy (230/423 (54.4%) and 5/6 (83.3%), respectively) compared to women. The average age of patients suffering from lesions with and without associated malignancy was 57 and 54 years, respectively. The common site of lesion alone was head and neck but lesions with malignancy involved lower extremities. The two lesions were significantly different in site of occurrence (p < 0.001). Conclusion: Generally, although the association between seborrheic keratosis and skin malignancy appears to be accidental, it must always be in mind. Therefore, histopathologic examination of all seborrheic keratosis should be considered, especially when seborrheic keratosis has atypical clinical manifestations. PMID:23267371

Keratosis pilaris and prevalence of acne vulgaris: a cross-sectional study.

PubMed

Schmitt, Juliano Vilaverde; Lima, Brunno Zeni de; Souza, Monique Carolina Meira do Rosário de; Miot, Hélio Amante

2014-01-01

Acne vulgaris has an important genetic predisposition, as well as keratosis pilaris. Clinical observations suggest that patients with keratosis pilaris have less frequent or less severe acne breakouts; however, we found no studies on this regard To determine if the presence of keratosis pilaris is associated with lower prevalence and severity of acne. A cross-sectional study was conducted with dermatology outpatients aged between 14 and 35 years. We evaluated history and clinical grade of acne, demographic variables, history of atopy, smoking, and use of hormonal contraceptives. Two groups were defined by the presence or absence of moderate to severe keratosis pilaris on the arms and were compared by bivariate analysis and by conditional multiple logistic regression. We included 158 patients (66% women), with a median age of 23 ± 11 years. Twenty-six percent of them had keratosis pilaris, which was associated with a history of atopy (odds ratio [OR]=2.80 [1.36 to 5.75]; p<0.01). Acne was present in 66% of subjects, and was related to family history of acne (OR=5.75 [2.47 to 13.37]; p<0.01). In bivariate and multivariate analysis, the group with keratosis pilaris had a less frequent history of acne (OR=0.32 [0.14 to 0.70]; p<0.01). The presence of moderate to severe keratosis pilaris on the arms was associated with lower prevalence of acne vulgaris and lower severity of facial lesions in adolescents and young adults.

Management of actinic cheilitis using ingenol mebutate gel: A report of seven cases.

PubMed

Flórez, Ángeles; Batalla, Ana; de la Torre, Carlos

2017-03-01

Actinic cheilitis (AC) can precede the development of squamous cell carcinoma of the lip, a location with high risk of invasiveness and metastasis. We communicate the good results that we obtained when treating seven patients suffering from AC with ingenol mebutate (IM) 0,015% concentration gel on three consecutive days. Three patients achieved complete clearance and four significant improvement. IM is a topical field treatment approved for actinic keratosis. To our knowledge, reported experience in the management of AC with IM is very limited. Local skin responses grade 3 were the main adverse event observed and they resolved in all patients without specific therapy within 1 to 2 weeks. IM is characterized by its rapid clinical effect, its favorable safety profile and its dosing period of only 3 days, shorter than with other field therapies. All these facts make it an attractive new therapy for AC, with need for further study.

Keratosis pilaris and prevalence of acne vulgaris: a cross-sectional study*

PubMed Central

Schmitt, Juliano Vilaverde; de Lima, Brunno Zeni; de Souza, Monique Carolina Meira do Rosário; Miot, Hélio Amante

2014-01-01

BACKGROUND Acne vulgaris has an important genetic predisposition, as well as keratosis pilaris. Clinical observations suggest that patients with keratosis pilaris have less frequent or less severe acne breakouts; however, we found no studies on this regard OBJECTIVE To determine if the presence of keratosis pilaris is associated with lower prevalence and severity of acne. METHODS A cross-sectional study was conducted with dermatology outpatients aged between 14 and 35 years. We evaluated history and clinical grade of acne, demographic variables, history of atopy, smoking, and use of hormonal contraceptives. Two groups were defined by the presence or absence of moderate to severe keratosis pilaris on the arms and were compared by bivariate analysis and by conditional multiple logistic regression. RESULTS We included 158 patients (66% women), with a median age of 23±11 years. Twenty-six percent of them had keratosis pilaris, which was associated with a history of atopy (odds ratio [OR]=2.80 [1.36 to 5.75]; p<0.01). Acne was present in 66% of subjects, and was related to family history of acne (OR=5.75 [2.47 to 13.37]; p<0.01). In bivariate and multivariate analysis, the group with keratosis pilaris had a less frequent history of acne (OR=0.32 [0.14 to 0.70]; p<0.01). CONCLUSION The presence of moderate to severe keratosis pilaris on the arms was associated with lower prevalence of acne vulgaris and lower severity of facial lesions in adolescents and young adults. PMID:24626653

Clinical and histopathologic study of benign lichenoid keratosis on the face.

PubMed

Kim, Han Su; Park, Eun Joo; Kwon, In Ho; Kim, Kwang Ho; Kim, Kwang Joong

2013-10-01

Benign lichenoid keratosis is a cutaneous entity that consists of a nonpruritic papule or slightly indurated plaque that is histologically characterized by a band-like inflammatory infiltrate with interface involvement. The purpose of this study was to investigate the clinical and histopathologic features of benign lichenoid keratosis localized on the face. Fourteen benign lichenoid keratosis patients diagnosed clinically and histopathologically in our clinic during the 10-year period from 2002 to 2012 were studied. Thirteen female and 1 male patients were included. The mean age at diagnosis was 46.5 years. The color of most of the lesions was brown (10 cases, 71%). The cheek was the most commonly involved area (10 cases, 71%). All of the lesions were single. There were 9 (64%) flat lesion cases and 5 (36%) raised lesion cases. Most patients denied having any symptoms; 3 had mild pruritus. The histopathological findings indicated that all the cases exhibited lichenoid inflammatory infiltrate obscuring the dermal-epidermal junction and vacuolar alteration of basal cell layer. The lesions showed focal parakeratosis (79%), melanophages (79%), hyperkeratosis (71%), and necrotic keratinocytes (71%). Solar elastosis (50%) and acanthosis (43%) were also seen frequently. Diagnosis of benign lichenoid keratosis should be made by a combination of clinical manifestations and histopathological findings. In particular, benign lichenoid keratosis should be considered if a middle-aged patient presents a solitary asymptomatic brown lesion on the face. We think benign lichenoid keratosis may be a specific disorder rather than the inflammatory stage of regressing solar lentigines, large cell acanthoma or reticulated seborrheic keratosis.

Lichenoid keratosis is frequently misdiagnosed as basal cell carcinoma.

PubMed

Maor, D; Ondhia, C; Yu, L L; Chan, J J

2017-08-01

Lichenoid keratosis (LK), also known as benign lichenoid keratosis or lichen planus-like keratosis, is a solitary, pink to red-brown scaly plaque representing a host immunological response to a variety of precursor lesions. LK is often misdiagnosed as a dermatological malignancy owing to its clinical resemblance to basal cell carcinoma (BCC) or Bowen disease. We performed a retrospective analysis of the pathology records of a series of LK lesions with reference to the demographic features and accuracy of clinical diagnosis. The pathology records from 2008 to 2009 of 263 consecutive patients with a histological diagnosis of LK from a specialized skin laboratory were retrieved. Data relating to clinical diagnosis, age, sex, anatomical location, time of year of presentation and any coexistent pathological lesions adjacent to the LK were recorded. Mean age at presentation was 64 years (range 34-96), and 58% of patients were female. The most common anatomical site was the chest/anterior torso, followed by the back and legs. The most common coexisting lesion was solar keratosis at 14%, followed by seborrhoeic keratosis (SK) at 7.8%. The correct clinical diagnosis of LK was made in 29.5% of cases. The most common clinical diagnosis was BCC (47%), while SK was the preferred diagnosis in 18%. A clinical diagnosis was not given in 5.5% of cases. In conclusion, it appears that LK is frequently misdiagnosed, with misdiagnosis occurring in > 70% of cases in this study. © 2017 British Association of Dermatologists.

Topical photodynamic therapy with 5-aminolevulinic acid in the treatment of actinic keratoses: a first clinical study

NASA Astrophysics Data System (ADS)

Karrer, Sigrid; Szeimies, Rolf-Markus; Sauerwald, Angela; Landthaler, Michael

1996-01-01

In this first clinical study performed according to GCP- (good clinical practice) guidelines, efficacy, and tolerability of topical photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) were tested in the treatment of actinic keratoses. Ten patients (6 f, 4 m) with 36 lesions (19 located on hands and arms, 17 on the head) received ALA-PDT once. Five to six hours after occlusive application of ALA (water-in-oil-emulsion containing 10% ALA) irradiation was performed with an incoherent light source. Up to 3 months after treatment patients were monitored. A score evaluating infiltration and keratosis of treated actinic keratoses allowed us to estimate therapeutic efficacy. Compared to the initial score (100%) significantly lower score-sums were observed at the 28 day follow-up at both localizations (head: 15%; hand: 67%). Complete remission (score sum 0) resulted in 71% of actinic keratoses localized on the head. Except for slight pain and burning sensations during and after irradiation there were no notable side effects. This study proved good efficacy and tolerability of topical PDT in the treatment of actinic keratoses. Whether PDT is able to compete with established treatment modalities remains to be shown in further studies.

Role of linoleic acid in arsenical palmar keratosis.

PubMed

Ahmed, Tarafder S; Misbahuddin, Mir

2016-03-01

Chronic arsenic exposure can lead to palmoplantar keratosis. In the stratum corneum of skin, linoleic acid is of the utmost importance to the inflammation, keratinization, and regeneration processes. The aims of this study were: (i) to present quantitative information on the linoleic acid fraction of intercorneocyte lipids, and (ii) to elucidate the role of linoleic acid in the pathophysiology of arsenical keratosis. Lipid extracts were collected from keratotic lesions in seven patients, seven arsenic-exposed subjects, and seven non-exposed control subjects. Linoleic acid levels of the specimens were estimated by reverse-phase high-performance liquid chromatography (RP-HPLC). There was a significant (P < 0.001) increase in mean ± standard error (SE) linoleic acid levels in arsenical keratosis patients (palm: 25.66 ± 4.95 μg/cm(2); dorsum: 28.25 ± 6.20 μg/cm(2)) compared with arsenic-exposed (palm: 2.75 ± 0.85 μg/cm(2); dorsum: 1.96 ± 0.64 μg/cm(2)) and non-exposed (palm: 1.52 ± 0.61 μg/cm(2); dorsum: 1.28 ± 0.39 μg/cm(2)) control subjects. There was no significant difference (P = 0.556) in linoleic acid concentration in the non-affected skin of the dorsum of the hand (28.25 ± 6.20 μg/cm(2)) compared with that in the palmar sites (25.66 ± 4.95 μg/cm(2)) in the patient group. The change in linoleic acid levels in the arsenic-exposed control group did not differ from that in non-exposed controls (P = 1.000). Linoleic acid concentration is elevated in arsenical keratosis; this finding warrants further investigation to ascertain whether linoleic acid plays a direct role in the pathophysiology of arsenical keratosis. © 2015 The International Society of Dermatology.

[Increased glucose uptake by seborrheic keratosis on PET scan].

PubMed

Merklen-Djafri, C; Truntzer, P; Hassler, S; Cribier, B

2017-05-01

Positron emission tomography (PET) is an examination based upon the uptake of a radioactive tracer by hypermetabolic cells. It is primarily used in tandem with tomodensitometry (PET-TDM) for cancer staging because of its high sensitivity and specificity for the detection of metastases. However, unusually high uptake may occur with benign tumours, including skin tumours. Herein, we report an extremely rare case of pathological uptake levels resulting from seborrhoeic keratosis. A 55-year-old male patient with oesophageal squamous-cell carcinoma was referred to us following the discovery of an area of high marker uptake following PET-TDM and corresponding to a pigmented skin lesion. No other areas of suspect high uptake were seen. The lesion was surgically excised and histological examination indicated seborrhoeic keratosis. The histological appearance was that of standard seborrhoeic keratosis without any notable mitotic activity. PET-TDM is an examination that enables diagnosis of malignancy. However, rare cases have been described of increased marker uptake by benign cutaneous tumours such as histiocytofibroma, pilomatricoma and condyloma. To date, there have only been only very few cases of increased uptake due to seborrhoeic keratosis. This extremely unusual case of increased glucose uptake in PET-TDM due to seborrhoeic keratosis confirms that the hypermetabolic activity detected by this examination is not necessarily synonymous with malignancy and that confirmation by clinical and histological findings is essential. The reasons for increased metabolic activity within such benign tumours are not known. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Efficacy of ablative fractional laser-assisted photodynamic therapy for the treatment of actinic cheilitis: 12-month follow-up results of a prospective, randomized, comparative trial.

PubMed

Choi, S H; Kim, K H; Song, K-H

2015-07-01

Early identification and treatment of actinic cheilitis (AC) is recommended. Although photodynamic therapy (PDT) is an attractive therapeutic option for AC, PDT for AC does not result in the same satisfactory outcomes as in actinic keratosis (AK). The aim of our study was to compare efficacy, recurrence rate, cosmetic outcome and safety between erbium:yttrium-aluminium-garnet ablative fractional laser-assisted methyl aminolaevulinate-PDT (Er:YAG AFL MAL-PDT) and standard MAL-PDT. Thirty-three patients with histologically confirmed AC randomly received either one session of Er:YAG AFL MAL-PDT or two sessions of MAL-PDT. In the MAL-PDT group, the second session of MAL-PDT was administered 7 days later. Patients were followed up at 1 week and 3 and 12 months, and biopsies were taken from all patients at 3 and 12 months after the last treatment session. At the final 12-month follow-up, cosmetic outcomes were assessed. Adverse events were assessed at week 1 of the treatment phase and every subsequent follow-up visit. In the per-protocol (PP) population, Er:YAG AFL MAL-PDT was significantly more effective (92% complete response rate) than MAL-PDT (59%; P = 0.040) at the 3-month follow-up, and differences in efficacy remained significant at the 12-month follow-up (85% in Er:YAG AFL MAL-PDT and 29% in MAL-PDT). The recurrence rate was significantly lower for Er:YAG AFL MAL-PDT (8%) than for MAL-PDT (50%) group at 12 months (P = 0.029). No significant difference in cosmetic outcome or safety was observed between Er:YAG AFL MAL-PDT and MAL-PDT. Ablative fractional laser pretreatment has significant benefit for the treatment of AC with PDT. © 2014 British Association of Dermatologists.

Neoplastic Multifocal Skin Lesions: Biology, Etiology, and Targeted Therapies for Nonmelanoma Skin Cancers.

PubMed

Fernandes, Ana R; Santos, Ana C; Sanchez-Lopez, Elena; Kovačević, Andjekla B; Espina, Marta; Calpena, Ana C; Veiga, Francisco J; Garcia, Maria L; Souto, Eliana B

2018-01-01

Neoplastic skin lesions are multifocal, diffuse skin infiltrations of particular relevance in the differential diagnosis of ulcerative, nodular, or crusting skin lesions. Nonmelanoma skin cancers (NMSCs), namely, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and also actinic keratosis (AK), are the most common malignant tumors in humans. BCCs do not proliferate rapidly and most of the times do not metastasize, while SCCs are more infiltrative, metastatic, and destructive. AKs are precursor lesions of cutaneous SCCs. The classical therapy of NMSCs makes use of photodynamic therapy associated with chemotherapeutics. With improved understanding of the pathological mechanisms of tumor initiation, progression, and differentiation, a case is made towards the use of targeted chemotherapy with the intent to reduce the cytotoxicity of classical treatments. The present review aims to describe the current state of the art on the knowledge of NMSC, including its risks factors, oncogenes, and skin carcinogenesis, discussing the classical therapy against new therapeutic options. © 2017 S. Karger AG, Basel.

Dermoscopy of keratinocyte skin cancer.

PubMed

Kupsa, Romana; Deinlein, Teresa; Woltsche, Nora; Hofmann-Wellenhof, Rainer; Zalaudek, Iris

2016-12-01

Keratinocyte skin cancer (KSC) refers to a broad class of tumors with a regrettably rising incidence worldwide. The term KSC stands for different stages of skin cancer including actinic keratosis (AK), Bowen's Disease (BD) and invasive squamous cell carcinoma (SCC). These tumors tend to grow slow, are unlikely to result in distant metastatic disease and death but they frequently destroy underlying tissues and should therefore be removed at the earliest possible stage. The fact that the cure rate is very high when KSC is detected in early stages emphasizes once more the applicability of dermoscopy as an integrative part of the clinical examination of skin tumors. In the first part of this review article, we summarize key points of the dermoscopic diagnosis of KSC including different stages of AK, BD and SCC. In the second part we want to focus on the progression model of KSC and the role of dermoscopy in the management of keratinocyte skin cancer.

Daylight methyl-aminolevulinate photodynamic therapy versus ingenol mebutate for the treatment of actinic keratoses: an intraindividual comparative analysis.

PubMed

Genovese, Giovanni; Fai, Dario; Fai, Carlotta; Mavilia, Luciano; Mercuri, Santo R

2016-05-01

Daylight-photodynamic therapy (D-PDT) and ingenol mebutate (IM) are novel therapies directed to actinic keratoses (AK). The purpose of our study was to compare effectiveness, tolerability, cosmetic outcome and patient preference of D-PDT versus IM in the treatment of grade I and II AK. Twenty-seven patients with AK on the face or scalp were enrolled. Each patient received, in a 25 cm(2) target area, D-PDT on right side and IM on left side. Overall 323 AK were treated. Both target areas achieved complete response in 40.47% of the cases and average AK clearance rate was similar for D-PDT and IM (p=0.74). In D-PDT areas mean grade II AK clearance rate was lower compared with that of grade I AK (p=0.015). In IM areas grade I and II AK average clearance rates were similar (p=0.28). At week 1 and month 1, mean local skin responses (LSR) score were higher in areas treated with IM. IM areas showed more severe pain and cosmetic sequelae. D-PDT had similar effectiveness to IM, even if IM demonstrated higher grade II AK clearance rate. Tolerability profile was superior for D-PDT in terms of LSR and pain. D-PDT was more cosmetically acceptable. Patients preferred D-PDT to IM in most cases. © 2016 Wiley Periodicals, Inc.

Actinic cheilitis: aesthetic and functional comparative evaluation of vermilionectomy using the classic and W-plasty techniques.

PubMed

Rossoe, Ed Wilson Tsuneo; Tebcherani, Antonio José; Sittart, José Alexandre; Pires, Mario Cezar

2011-01-01

Chronic actinic cheilitis is actinic keratosis located on the vermilion border. Treatment is essential because of the potential for malignant transformation. To evaluate the aesthetic and functional results of vermilionectomy using the classic and W-plasty techniques in actinic cheilitis. In the classic technique, the scar is linear and in the W-plasty one, it is a broken line. 32 patients with clinical and histopathological diagnosis of actinic cheilitis were treated. Out of the 32 patients, 15 underwent the W-plasty technique and 17 underwent the classic one. We evaluated parameters such as scar retraction and functional changes. A statistically significant association between the technique used and scar retraction was found, which was positive when using the classic technique (p = 0.01 with Yates' correction). The odds ratio was calculated at 11.25, i.e., there was a greater chance of retraction in patients undergoing the classic technique. Both techniques revealed no functional changes. We evaluated postoperative complications such as the presence of crusts, dry lips, paresthesia, and suture dehiscence. There was no statistically significant association between complications and the technique used (p = 0.69). We concluded that vermilionectomy using the W-plasty technique shows better cosmetic results and similar complication rates.

Association between melanocytic neoplasms and seborrheic keratosis: more than a coincidental collision?

PubMed Central

DeFazio, Jennifer; Zalaudek, Iris; Busam, Klaus J.; Cota, Carlo; Marghoob, Ashfaq

2012-01-01

Clinical observations and an expanding knowledge of cell-to-cell communication have led us to speculate that the finding of a melanocytic nevus in conjunction with a seborrheic keratosis is more than a coincidental collision of two lesions. Here we present five cases demonstrating dermoscopic features of both melanocytic lesions and seborrheic keratoses with corresponding histology. Four cases demonstrate dermoscopic features of a melanocytic nevus and seborrheic keratosis, and the final case a melanoma arising in association with a seborrheic keratosis. PMID:23785597

Keratosis Pilaris Revisited: Is It More Than Just a Follicular Keratosis?

PubMed Central

Thomas, Mary; Khopkar, Uday Sharadchandra

2012-01-01

Background: Keratosis pilaris (KP) is characterized by keratinous plugs in the follicular orifices and varying degrees of perifollicular erythema. The most accepted theory of its pathogenesis proposes defective keratinization of the follicular epithelium resulting in a keratotic infundibular plug. We decided to test this hypothesis by doing dermoscopy of patients diagnosed clinically as keratosis pilaris. Materials and Methods: Patients with a clinical diagnosis of KP seen between September 2011 and December 2011 were included in the study. A clinical history was obtained and examination and dermoscopic evaluation were performed on the lesions of KP. Results: The age of the patients ranged from 6-38 years. Sixteen patients had history of atopy. Nine had concomitant ichthyosis vulgaris. All the 25 patients were found to have coiled hair shafts within the affected follicular infundibula. The hair shafts were extracted with the help of a sterile needle and were found to retain their coiled nature. Perifollicular erythema was seen in 11 patients; perifollicular scaling in 9. Conclusion: Based on our observations and previously documented histological data of KP, we infer that KP may not be a disorder of keratinization, but caused by the circular hair shaft which ruptures the follicular epithelium leading to inflammation and abnormal follicular keratinization. PMID:23766609

Clinical study of noninvasive in vivo melanoma and nonmelanoma skin cancers using multimodal spectral diagnosis

PubMed Central

Lim, Liang; Nichols, Brandon; Migden, Michael R.; Rajaram, Narasimhan; Reichenberg, Jason S.; Markey, Mia K.; Ross, Merrick I.; Tunnell, James W.

2014-01-01

Abstract. The goal of this study was to determine the diagnostic capability of a multimodal spectral diagnosis (SD) for in vivo noninvasive disease diagnosis of melanoma and nonmelanoma skin cancers. We acquired reflectance, fluorescence, and Raman spectra from 137 lesions in 76 patients using custom-built optical fiber-based clinical systems. Biopsies of lesions were classified using standard histopathology as malignant melanoma (MM), nonmelanoma pigmented lesion (PL), basal cell carcinoma (BCC), actinic keratosis (AK), and squamous cell carcinoma (SCC). Spectral data were analyzed using principal component analysis. Using multiple diagnostically relevant principal components, we built leave-one-out logistic regression classifiers. Classification results were compared with histopathology of the lesion. Sensitivity/specificity for classifying MM versus PL (12 versus 17 lesions) was 100%/100%, for SCC and BCC versus AK (57 versus 14 lesions) was 95%/71%, and for AK and SCC and BCC versus normal skin (71 versus 71 lesions) was 90%/85%. The best classification for nonmelanoma skin cancers required multiple modalities; however, the best melanoma classification occurred with Raman spectroscopy alone. The high diagnostic accuracy for classifying both melanoma and nonmelanoma skin cancer lesions demonstrates the potential for SD as a clinical diagnostic device. PMID:25375350

Clinical study of noninvasive in vivo melanoma and nonmelanoma skin cancers using multimodal spectral diagnosis

NASA Astrophysics Data System (ADS)

Lim, Liang; Nichols, Brandon; Migden, Michael R.; Rajaram, Narasimhan; Reichenberg, Jason S.; Markey, Mia K.; Ross, Merrick I.; Tunnell, James W.

2014-11-01

The goal of this study was to determine the diagnostic capability of a multimodal spectral diagnosis (SD) for in vivo noninvasive disease diagnosis of melanoma and nonmelanoma skin cancers. We acquired reflectance, fluorescence, and Raman spectra from 137 lesions in 76 patients using custom-built optical fiber-based clinical systems. Biopsies of lesions were classified using standard histopathology as malignant melanoma (MM), nonmelanoma pigmented lesion (PL), basal cell carcinoma (BCC), actinic keratosis (AK), and squamous cell carcinoma (SCC). Spectral data were analyzed using principal component analysis. Using multiple diagnostically relevant principal components, we built leave-one-out logistic regression classifiers. Classification results were compared with histopathology of the lesion. Sensitivity/specificity for classifying MM versus PL (12 versus 17 lesions) was 100%;/100%;, for SCC and BCC versus AK (57 versus 14 lesions) was 95%;/71%, and for AK and SCC and BCC versus normal skin (71 versus 71 lesions) was 90%/85%. The best classification for nonmelanoma skin cancers required multiple modalities; however, the best melanoma classification occurred with Raman spectroscopy alone. The high diagnostic accuracy for classifying both melanoma and nonmelanoma skin cancer lesions demonstrates the potential for SD as a clinical diagnostic device.

Low-dose 5-fluorouracil in combination with salicylic acid for the treatment of actinic keratoses on the hands and/or forearms - results of a non-interventional study.

PubMed

Reinhold, U; Hadshiew, I; Melzer, A; Prechtl, A

2017-03-01

As an in situ carcinoma, actinic keratoses should be treated early. Previous studies on the efficacy of a low-dose 0.5% 5-fluorouracil solution in combination with 10% salicylic acid (low-dose 5-FU/SA) are mostly related to lesions appearing on the head and face. In contrast, actinic keratoses (AK) lesions of the upper extremities are considered to be difficult to treat. The efficacy of low-dose 5-FU/SA in the treatment of actinic keratoses on the hands and/or forearms was studied for the first time in this non-interventional study (NIS) under practical conditions in a large patient population. In addition to the clinical course during therapy and a follow-up period, the length of application and adherence were documented. As part of this NIS, 649 patients with AK were treated at 207 centres with low-dose 5-FU/SA. The data of the study were recorded at baseline, optionally during an intermediate examination, at the end of therapy and during a final assessment. The average number of AK lesions decreased during the entire observation period by 92%. Side-effects were documented only rarely in the form of local skin reactions (2%). The attending physicians assessed the efficacy, tolerability and safety of the therapy as being predominantly very good or good (in each case ≥90%). AK lesions on the hands and/or forearms were effectively treated with low-dose 5-FU/SA under routine conditions in dermatological practice and the treatment was well tolerated. © 2016 European Academy of Dermatology and Venereology.

46 CFR 7.175 - Alaska Peninsula, AK to Nunivak, AK.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Alaska Peninsula, AK to Nunivak, AK. 7.175 Section 7.175 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.175 Alaska Peninsula, AK to Nunivak, AK. (a) A line drawn from the northernmost extremity of...

46 CFR 7.175 - Alaska Peninsula, AK to Nunivak, AK.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 1 2012-10-01 2012-10-01 false Alaska Peninsula, AK to Nunivak, AK. 7.175 Section 7.175 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.175 Alaska Peninsula, AK to Nunivak, AK. (a) A line drawn from the northernmost extremity of...

46 CFR 7.175 - Alaska Peninsula, AK to Nunivak, AK.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 1 2014-10-01 2014-10-01 false Alaska Peninsula, AK to Nunivak, AK. 7.175 Section 7.175 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.175 Alaska Peninsula, AK to Nunivak, AK. (a) A line drawn from the northernmost extremity of...

46 CFR 7.175 - Alaska Peninsula, AK to Nunivak, AK.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Alaska Peninsula, AK to Nunivak, AK. 7.175 Section 7.175 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.175 Alaska Peninsula, AK to Nunivak, AK. (a) A line drawn from the northernmost extremity of...

46 CFR 7.175 - Alaska Peninsula, AK to Nunivak, AK.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 1 2013-10-01 2013-10-01 false Alaska Peninsula, AK to Nunivak, AK. 7.175 Section 7.175 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.175 Alaska Peninsula, AK to Nunivak, AK. (a) A line drawn from the northernmost extremity of...

Anogenital giant seborrheic keratosis.

PubMed

Wollina, Uwe; Chokoeva, Anastasiya; Tchernev, Georgi; Heinig, Birgit; Schönlebe, Jacqueline

2017-08-01

Seborrheic keratosis (SK) are very common benign epidermal tumors. Giant seborrheic keratosis (GSK) is a rare variant with clinical characteristics, which leads very often to misdiagnosis. A genital site of SK is very unusual clinical manifestation and although the cause is still unknown, current literature data point to a possible pathogenetic role of chronic friction and HPV infection. The rare genital localization makes Buschke-Löwenstein tumor and verrucous carcinoma important differential diagnoses. GSK may also show some clinical features of a melanoacanthoma, which makes cutaneous melanoma as another possible differential diagnosis. The clinical diagnosis of genital GSK is often a very difficult one, because the typical clinical features of GSK disappear and the most common dermoscopic features of GSK are usually not seen in the genital region lesions. The diagnosis of GSK of the anogenital area should be made only and always after the exact histological verification and variety of differential diagnosis should be carefully considered. The treatment of GSK is primary surgically. We present a rare case of GSK with concomitant HPV infection in the anogenital region of 72-year-old patient. Surgical approach was performed with excellent outcome.

Apple S-RNase interacts with an actin-binding protein, MdMVG, to reduce pollen tube growth by inhibiting its actin-severing activity at the early stage of self-pollination induction.

PubMed

Yang, Qing; Meng, Dong; Gu, Zhaoyu; Li, Wei; Chen, Qiuju; Li, Yang; Yuan, Hui; Yu, Jie; Liu, Chunsheng; Li, Tianzhong

2018-04-18

In S-RNase-mediated self-incompatibility, S-RNase secreted from the style destroys the actin cytoskeleton of the self-pollen tubes, eventually halting their growth, but the mechanism of this process remains unclear. In vitro biochemical assays revealed that S-RNase does not bind or sever filamentous actin (F-actin). In apple (Malus domestica), we identified an actin-binding protein containing myosin, villin and GRAM (MdMVG), that physically interacts with S-RNase and directly binds and severs F-actin. Immunofluorescence assays and total internal reflection fluorescence microscopy indicated that S-RNase inhibits the F-actin-severing activity of MdMVG in vitro. In vivo, the addition of S-RNase to self-pollen tubes increased the fluorescence intensity of actin microfilaments and reduced the severing frequency of microfilaments and the rate of pollen tube growth in self-pollination induction in the presence of MdMVG overexpression. By generating 25 single-, double- and triple-point mutations in the amino acid motif E-E-K-E-K of MdMVG via mutagenesis and testing the resulting mutants with immunofluorescence, we identified a triple-point mutant, MdMVG (E167A/E171A/K185A) , that no longer has F-actin-severing activity or interacts with any of the four S-haplotype S-RNases, indicating that all three amino acids (E167, E171 and K185) are essential for the severing activity of MdMVG and its interaction with S-RNases. We conclude that apple S-RNase interacts with MdMVG to reduce self-pollen tube growth by inhibiting its F-actin-severing activity. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

46 CFR 7.170 - Alaska Peninsula, AK to Aleutian Islands, AK.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 1 2014-10-01 2014-10-01 false Alaska Peninsula, AK to Aleutian Islands, AK. 7.170 Section 7.170 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.170 Alaska Peninsula, AK to Aleutian Islands, AK. (a) A line drawn from the...

46 CFR 7.165 - Kenai Peninsula, AK to Kodiak Island, AK.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 1 2012-10-01 2012-10-01 false Kenai Peninsula, AK to Kodiak Island, AK. 7.165 Section 7.165 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.165 Kenai Peninsula, AK to Kodiak Island, AK. (a) A line drawn from the...

46 CFR 7.170 - Alaska Peninsula, AK to Aleutian Islands, AK.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Alaska Peninsula, AK to Aleutian Islands, AK. 7.170 Section 7.170 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.170 Alaska Peninsula, AK to Aleutian Islands, AK. (a) A line drawn from the...

46 CFR 7.165 - Kenai Peninsula, AK to Kodiak Island, AK.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 1 2013-10-01 2013-10-01 false Kenai Peninsula, AK to Kodiak Island, AK. 7.165 Section 7.165 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.165 Kenai Peninsula, AK to Kodiak Island, AK. (a) A line drawn from the...

46 CFR 7.165 - Kenai Peninsula, AK to Kodiak Island, AK.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 1 2014-10-01 2014-10-01 false Kenai Peninsula, AK to Kodiak Island, AK. 7.165 Section 7.165 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.165 Kenai Peninsula, AK to Kodiak Island, AK. (a) A line drawn from the...

46 CFR 7.165 - Kenai Peninsula, AK to Kodiak Island, AK.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Kenai Peninsula, AK to Kodiak Island, AK. 7.165 Section 7.165 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.165 Kenai Peninsula, AK to Kodiak Island, AK. (a) A line drawn from the...

46 CFR 7.165 - Kenai Peninsula, AK to Kodiak Island, AK.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Kenai Peninsula, AK to Kodiak Island, AK. 7.165 Section 7.165 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.165 Kenai Peninsula, AK to Kodiak Island, AK. (a) A line drawn from the...

46 CFR 7.170 - Alaska Peninsula, AK to Aleutian Islands, AK.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 1 2013-10-01 2013-10-01 false Alaska Peninsula, AK to Aleutian Islands, AK. 7.170 Section 7.170 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.170 Alaska Peninsula, AK to Aleutian Islands, AK. (a) A line drawn from the...

Regulatory T cells in the actinic cheilitis.

PubMed

Gasparoto, Thaís Helena; de Souza Malaspina, Tatiana Salles; Damante, José Humberto; de Mello, Edgard Franco; Ikoma, Maura Rosane Valério; Garlet, Gustavo Pompermaier; Costa, Maria Renata Sales Nogueira; Cavassani, Karen Angélica; da Silva, João Santana; Campanelli, Ana Paula

2014-11-01

Actinic cheilitis (AC) is an oral potentially malignant lesion which is the counterpart of actinic keratosis of the skin and has potential to develop into squamous cell carcinoma. Regulatory T cells (Tregs) have a critical role in modulating the antitumor immune responses. The presence of regulatory T cells in potentially malignant lesions has not been described. We chose investigate the involvement of regulatory T cells in potentially malignant lesions. The frequency, phenotype, and activity of CD4+CD25+ T cells isolated from blood and lesion of AC patients were analyzed by flow cytometry. Cytokines were quantified by ELISA. Data were compared with samples from healthy subjects. The frequency and suppressor activity of circulating CD4+CD25+ T cells was similar in AC patients and control subjects. However, the frequencies of IL-10-positive Tregs were higher in AC patients, and these cells inhibited interferon-gamma (IFN-γ) and increased interleukin (IL)-10 productions in co-cultures. Furthermore, CD4+CD25+ T cells accumulate in AC lesions. Lesions-derived regulatory T cells suppressed lymphocyte proliferation and pro-inflammatory cytokine production. Moreover, high levels of IL-10 and transforming growth factor-β (TGF-β), and low IFN-γ were detected in the potentially malignant lesions. Therefore, our data show that Tregs accumulate in AC lesions, and these cells could be suppressing immune responses in a potentially malignant microenvironment. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

46 CFR 7.160 - Point Whitshed, AK to Aialik Cape, AK.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Point Whitshed, AK to Aialik Cape, AK. 7.160 Section 7.160 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.160 Point Whitshed, AK to Aialik Cape, AK. (a) A line drawn from the southernmost...

46 CFR 7.160 - Point Whitshed, AK to Aialik Cape, AK.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Point Whitshed, AK to Aialik Cape, AK. 7.160 Section 7.160 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.160 Point Whitshed, AK to Aialik Cape, AK. (a) A line drawn from the southernmost...

46 CFR 7.160 - Point Whitshed, AK to Aialik Cape, AK.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 1 2013-10-01 2013-10-01 false Point Whitshed, AK to Aialik Cape, AK. 7.160 Section 7.160 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.160 Point Whitshed, AK to Aialik Cape, AK. (a) A line drawn from the southernmost...

46 CFR 7.160 - Point Whitshed, AK to Aialik Cape, AK.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 1 2012-10-01 2012-10-01 false Point Whitshed, AK to Aialik Cape, AK. 7.160 Section 7.160 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.160 Point Whitshed, AK to Aialik Cape, AK. (a) A line drawn from the southernmost...

46 CFR 7.160 - Point Whitshed, AK to Aialik Cape, AK.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 1 2014-10-01 2014-10-01 false Point Whitshed, AK to Aialik Cape, AK. 7.160 Section 7.160 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.160 Point Whitshed, AK to Aialik Cape, AK. (a) A line drawn from the southernmost...

Non-invasive diagnosis and monitoring of actinic cheilitis with reflectance confocal microscopy.

PubMed

Ulrich, M; González, S; Lange-Asschenfeldt, B; Roewert-Huber, J; Sterry, W; Stockfleth, E; Astner, S

2011-03-01

Actinic cheilitis (AC) represents the equivalent of actinic keratosis on the lip. Various treatment modalities are available and the efficacy of diclofenac in hyaluronic acid has recently been described. Reflectance confocal microscopy (RCM) is a non-invasive imaging technique which has recently been applied for the diagnosis of actinic keratoses. Herein, we describe the applicability of RCM for the diagnosis of AC and for monitoring of treatment response of AC to diclofenac in hyaluronic acid. Ten Caucasian patients with clinical suspicion for AC were included in this study. To obtain a non-invasive diagnosis, RCM was performed at baseline, followed by biopsy and respective confocal-histopathological correlation. Six patients with a histological diagnosis of AC were treated with diclofenac in hyaluronic acid, whereby monitoring was performed by RCM. Reflectance confocal microscopy was able to correctly identify 6/7 cases of AC and 3/3 cases of benign lesions. The most important RCM criteria for diagnosis of AC were cellular atypia at the stratum spinosum and granulosum with atypical honeycomb pattern. One patient with AC was misclassified as inflammatory cheilitis by RCM as it showed marked inflammatory response and lacked clear signs of cellular atypia on RCM imaging. Following topical treatment with diclofenac gel, 5/6 patients (83%) showed a good treatment response with regression of dysplasia on consecutive RCM examination. Reflectance confocal microscopy is a promising tool for the non-invasive diagnosis and monitoring of actinic cheilitis. However, marked inflammation represents a potential diagnostic pitfall. In this regard, biopsy should be performed in doubtful cases. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

Actin, actin-binding proteins, and actin-related proteins in the nucleus.

PubMed

Kristó, Ildikó; Bajusz, Izabella; Bajusz, Csaba; Borkúti, Péter; Vilmos, Péter

2016-04-01

Extensive research in the past decade has significantly broadened our view about the role actin plays in the life of the cell and added novel aspects to actin research. One of these new aspects is the discovery of the existence of nuclear actin which became evident only recently. Nuclear activities including transcriptional activation in the case of all three RNA polymerases, editing and nuclear export of mRNAs, and chromatin remodeling all depend on actin. It also became clear that there is a fine-tuned equilibrium between cytoplasmic and nuclear actin pools and that this balance is ensured by an export-import system dedicated to actin. After over half a century of research on conventional actin and its organizing partners in the cytoplasm, it was also an unexpected finding that the nucleus contains more than 30 actin-binding proteins and new classes of actin-related proteins which are not able to form filaments but had evolved nuclear-specific functions. The actin-binding and actin-related proteins in the nucleus have been linked to RNA transcription and processing, nuclear transport, and chromatin remodeling. In this paper, we attempt to provide an overview of the wide range of information that is now available about actin, actin-binding, and actin-related proteins in the nucleus.

Treatment of pigmented keratosis pilaris in Asian patients with a novel Q-switched Nd:YAG laser.

PubMed

Kim, Sangeun

2011-06-01

Treatment for most cases of keratosis pilaris requires simple reassurance and general skin care recommendations. Many Asian patients find lesions due to pigmented keratosis pilaris to be cosmetically unappealing. Treatment of post-inflammatory hyperpigmentation using a 1064-nm Q-switched Nd:YAG laser with low fluence is reported. To investigate the efficacy of a novel Q-switched Nd:YAG laser for the treatment of pigmented keratosis pilaris in Asian patients. Ten patients with pigmented keratosis pilaris underwent five weekly treatments using a Q-switched Nd:YAG laser (RevLite(®); HOYA ConBio(®), Freemont, CA, USA) at 1064 nm with a 6-mm spot size and a fluence of 5.9 J/cm(2). Photographic documentation was obtained at baseline and 2 months after the final treatment. Clinical improvement was achieved in all 10 patients with minimal adverse effects. For the treatment of keratosis pilaris, the use of a Q-switched Nd:YAG laser can be helpful for improving cosmetic appearance as it can improve pigmentation.

46 CFR 7.155 - Cape Spencer, AK to Cape St. Elias, AK.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Cape Spencer, AK to Cape St. Elias, AK. 7.155 Section 7.155 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.155 Cape Spencer, AK to Cape St. Elias, AK. (a) A line drawn from the westernmost...

46 CFR 7.155 - Cape Spencer, AK to Cape St. Elias, AK.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Cape Spencer, AK to Cape St. Elias, AK. 7.155 Section 7.155 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.155 Cape Spencer, AK to Cape St. Elias, AK. (a) A line drawn from the westernmost...

46 CFR 7.155 - Cape Spencer, AK to Cape St. Elias, AK.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 1 2012-10-01 2012-10-01 false Cape Spencer, AK to Cape St. Elias, AK. 7.155 Section 7.155 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.155 Cape Spencer, AK to Cape St. Elias, AK. (a) A line drawn from the westernmost...

46 CFR 7.155 - Cape Spencer, AK to Cape St. Elias, AK.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 1 2014-10-01 2014-10-01 false Cape Spencer, AK to Cape St. Elias, AK. 7.155 Section 7.155 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.155 Cape Spencer, AK to Cape St. Elias, AK. (a) A line drawn from the westernmost...

46 CFR 7.155 - Cape Spencer, AK to Cape St. Elias, AK.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 1 2013-10-01 2013-10-01 false Cape Spencer, AK to Cape St. Elias, AK. 7.155 Section 7.155 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.155 Cape Spencer, AK to Cape St. Elias, AK. (a) A line drawn from the westernmost...

Insight into the number of pre-malignancies and malignancies of the skin in a hospital population in the Netherlands.

PubMed

van Rijsingen, Margit; Seubring, Inge; Maessen-Visch, Birgitte; Lavrijsen, Sjan; van Bergen, Bert; Groenewoud, Johannes; Gerritsen, Marie-Jeanne

2015-01-01

Skin cancer incidence is rising, placing a burden on healthcare systems worldwide. This problem may even be more extensive than expected, since registration of (pre)malignancies of the skin is poor. To provide insight into the numbers of (pre)malignancies in patients with actinic keratosis (AK) or basal cell carcinoma (BCC) in 2 university and 2 general hospitals. The types and numbers of previous tumours and of tumours during a two-year follow-up were collected from 574 patients. Mean time between the first diagnosed (pre)malignancy and time of inclusion was 6.6 years. Overall, 60% had multiple types of (pre)malignancies. In BCC patients, 61% had multiple BCCs, in patients with squamous cell carcinoma (SCC), 40% had multiple SCCs. The combination 'BCC and SCC' occurred in 10%, 'BCC and AK' in 47%, 'SCC and AK' in 14%. High numbers of patients with multiple (pre)malignancies were found in this patient population in university and general hospitals, which may well reflect the Dutch hospital population. We conclude that skin cancer patients are more extensively affected than was expected up till now. Consequently, the management of skin cancer may be in need of adaptation in near future and the question arises whether dermatologists have the capacity for providing care for all these patients.

Overexpression of Amyloid Precursor Protein Promotes the Onset of Seborrhoeic Keratosis and is Related to Skin Ageing.

PubMed

Li, Yuanying; Wang, Yu; Zhang, Wei; Jiang, Leiwei; Zhou, Wenming; Liu, Zhi; Li, Shijun; Lu, Hongguang

2018-02-28

Seborrhoeic keratosis is an age-related skin disease. Amyloid precursor protein (APP) plays an important role in the pathogenesis of age-related Alzheimer's disease. The aim of this study was to elucidate the expression characteristics of APP in seborrhoeic keratosis tissues (n = 50), and explore whether the production of APP is related to the onset of seborrhoeic keratosis and skin ageing, including ultraviolet (UV)-induced ageing, as observed in normal skin (n = 79). The results of immunohistochemistry, Western blotting and quantitative real-time PCR showed that APP and its downstream products (i.e. amyloid-β42) were more highly expressed in seborrhoeic keratosis than in paired adjacent normal skin tissues. In contrast, the expression of its key secretase (i.e. β-secretase1) was generally low. Furthermore, APP expression was higher in UV-exposed than non-exposed skin sites, and expression in the older age group (61-85 years) was greater than that in the younger age group (41-60 years) in seborrhoeic keratosis tissues (p<0.05). APP expression correlated positively with age in epidermis (p<0.05), but not in dermis. These findings suggest that overexpression of APP may promote the onset of seborrhoeic keratosis and is a marker of skin ageing and UV damage. Further research will elucidate whether therapeutic mitigation of increased levels of APP in the skin might delay the onset of seborrhoeic keratosis and skin ageing.

Actinous enigma or enigmatic actin

PubMed Central

Povarova, Olga I; Uversky, Vladimir N; Kuznetsova, Irina M; Turoverov, Konstantin K

2014-01-01

Being the most abundant protein of the eukaryotic cell, actin continues to keep its secrets for more than 60 years. Everything about this protein, its structure, functions, and folding, is mysteriously counterintuitive, and this review represents an attempt to solve some of the riddles and conundrums commonly found in the field of actin research. In fact, actin is a promiscuous binder with a wide spectrum of biological activities. It can exist in at least three structural forms, globular, fibrillar, and inactive (G-, F-, and I-actin, respectively). G-actin represents a thermodynamically instable, quasi-stationary state, which is formed in vivo as a result of the energy-intensive, complex posttranslational folding events controlled and driven by cellular folding machinery. The G-actin structure is dependent on the ATP and Mg2+ binding (which in vitro is typically substituted by Ca2+) and protein is easily converted to the I-actin by the removal of metal ions and by action of various denaturing agents (pH, temperature, and chemical denaturants). I-actin cannot be converted back to the G-form. Foldable and “natively folded” forms of actin are always involved in interactions either with the specific protein partners, such as Hsp70 chaperone, prefoldin, and the CCT chaperonin during the actin folding in vivo or with Mg2+ and ATP as it takes place in the G-form. We emphasize that the solutions for the mysteries of actin multifunctionality, multistructurality, and trapped unfolding can be found in the quasi-stationary nature of this enigmatic protein, which clearly possesses many features attributed to both globular and intrinsically disordered proteins. PMID:28232879

Arsenic-related Bowen's disease, palmar keratosis, and skin cancer.

PubMed Central

Cöl, M; Cöl, C; Soran, A; Sayli, B S; Oztürk, S

1999-01-01

Chronic arsenical intoxication can still be found in environmental and industrial settings. Symptoms of chronic arsenic intoxication include general pigmentation or focal "raindrop" pigmentation of the skin and the appearance of hyperkeratosis of the palms of the hands and soles of the feet. In addition to arsenic-related skin diseases including keratosis, Bowen's disease, basal-cell-carcinoma, and squamous-cell carcinoma, there is also an increased risk of some internal malignancies. Arsenic-related diseases are common in areas of the world where the drinking water has a high arsenic content. In this paper, we describe a 35-year-old male patient who had arsenic-related keratosis, squamous-cell carcinoma in the palmar area of his left hand, and Bowen's disease on his left thigh. The patient worked in a borax mine for 15 years, so he was exposed to arsenic in drinking water, airborne arsenic in his workplace, and had direct contact. The patient was treated for 11 months for arsenic-related keratosis until an axillary lymph node metastasis occurred; the lesion was excised and diagnosed to be malignant. Bowen's disease was detected when the patient was being treated for cancer. No other malignancy was found. The patient is still receiving regular follow-up care. Images Figure 1 Figure 2 PMID:10417369

Mutational analysis of cutaneous squamous cell carcinomas and verrucal keratosis in patients taking BRAF inhibitors.

PubMed

Anforth, Rachael; Tembe, Varsha; Blumetti, Tatiana; Fernandez-Peñas, Pablo

2012-09-01

B-RAF inhibitors (BRAFi) have been shown to improve rates of overall and progression-free survival in patients with stage IV metastatic melanoma positive for the BRAF V600E mutation. However, the main drawback is the development of verrucal keratosis (hyperkeratotic papules with verruca-like characteristics with benign histological findings) and cutaneous squamous cell carcinomas (cuSCC). We have found upstream mutations in RAS as well as PIK3CA in both verrucal keratosis and cuSCC. This suggests that verrucal keratosis is an early clinical presentation of cuSCC in patients on BRAFi. © 2012 John Wiley & Sons A/S.

Actin-induced dimerization of palladin promotes actin-bundling

PubMed Central

Vattepu, Ravi; Yadav, Rahul; Beck, Moriah R

2015-01-01

A subset of actin binding proteins is able to form crosslinks between two or more actin filaments, thus producing structures of parallel or networked bundles. These actin crosslinking proteins interact with actin through either bivalent binding or dimerization. We recently identified two binding sites within the actin binding domain of palladin, an actin crosslinking protein that plays an important role in normal cell adhesion and motility during wound healing and embryonic development. In this study, we show that actin induces dimerization of palladin. Furthermore, the extent of dimerization reflects earlier comparisons of actin binding and bundling between different domains of palladin. On the basis of these results we hypothesized that actin binding may promote a conformational change that results in dimerization of palladin, which in turn may drive the crosslinking of actin filaments. The proximal distance between two actin binding sites on crosslinking proteins determines the ultrastructural properties of the filament network, therefore we also explored interdomain interactions using a combination of chemical crosslinking experiments and actin cosedimentation assays. Limited proteolysis data reveals that palladin is less susceptible to enzyme digestion after actin binding. Our results suggest that domain movements in palladin are necessary for interactions with actin and are induced by interactions with actin filaments. Accordingly, we put forth a model linking the structural changes to functional dynamics. PMID:25307943

Topical methyl-aminolevulinate photodynamic therapy using red light-emitting diode light for treatment of multiple actinic keratoses: A randomized, double-blind, placebo-controlled study.

PubMed

Pariser, David; Loss, Robert; Jarratt, Michael; Abramovits, William; Spencer, James; Geronemus, Roy; Bailin, Philip; Bruce, Suzanne

2008-10-01

The use of light-emitting diode light offers practical advantages in photodynamic therapy (PDT) with topical methyl-aminolevulinate (MAL) for management of actinic keratoses (AK). We sought to evaluate the efficacy of MAL PDT using red light-emitting diode light. We conducted a multicenter, double-blind, randomized study. A total of 49 patients with 363 AK lesions had 16.8% MAL cream applied under occlusion for 3 hours, and 47 patients with 360 AK lesions had vehicle cream similarly applied. The lesions were then illuminated (630 nm, light dose 37 J/cm2) with repeated treatment 1 week later. Complete lesion and patient (all lesions showing complete response) response rates were evaluated 3 months after last treatment. MAL PDT was superior (P<.0001) to vehicle PDT with respect to lesion complete response (86.2% vs 52.2%, odds ratio 6.9 [95% confidence interval 4.7-10.3]) and patient complete response (59.2% vs 14.9%, odds ratio 13.2 [95% confidence interval 4.1-43.1]). The study population may not be representative of all patients with AK. MAL PDT using red light-emitting diode light is an appropriate treatment alternative for multiple AK lesions.

[Arsenical keratosis treated by dermatome shaving].

PubMed

Kjerkegaard, Ulrik Knap; Heje, Jens Martin; Vestergaard, Christian; Stausbøl-Grøn, Birgitte; Stolle, Lars Bjørn

2014-05-05

Cutaneous malignancy in association with arsenic exposure is a rare but well-documented phenomenon. Signs of chronic arsenic exposure are very rare in Denmark today. However, arsenic was used in the medical treatment of psoriasis vulgaris up till the 1980's and several patients suffer from this arsenic treatment today. This case report shows that arsenical keratosis can be treated by dermatome shaving, a superficial destructive therapy.

A prospective, randomised, within-subject study of ALA-PDT for actinic keratoses using different irradiation regimes.

PubMed

Zaar, O; Sjöholm Hylén, A; Gillstedt, M; Paoli, J

2018-05-12

Photodynamic therapy (PDT) can be used to treat large fields of actinic keratoses (AKs) with high clearance rates. A notable downside is the amount of pain that accompany the treatment. This study aimed to optimise the illumination protocol during conventional PDT in order to reduce pain without compromising treatment effectiveness. In this prospective, randomised study with a split-face design, patients with, symmetrically distributed AKs were included. All patients were treated using a ALA 78 mg/g gel. One side was illuminated with the Aktilite ® CL-128 lamp and the other side with the RhodoLED ® lamp in which the light intensity gradually increased to a maximum of 60%. Both sides received a total light dose of 37 J/cm 2 . Pain during the treatment was measured using a visual analogue scale. The clinical effectiveness of the two treated sides was assessed after 12 weeks. 29 patients with 399 AKs were included. Illumination with the gradually increasing light intensity resulted in a decrease of the median VAS score by 1.1 points. Clearance rates were similar between the two lamps. Minimising the light intensity during the illumination phase of PDT reduces pain, while still preserving a high clearance rate of AKs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Diclofenac Topical (actinic keratosis)

MedlinePlus

... growths on the skin caused by too much sun exposure). Diclofenac is in a class of medications ... plan to avoid exposure to real and artificial sunlight (sun lamps) and to wear protective clothing and ...

Photodynamic Therapy Effectively Treats Actinic Keratoses Without Pre-Illumination Incubation Time.

PubMed

Gandy, Jessica; Labadie, Brian; Bierman, Dina; Zachary, Christopher

2017-03-01

BACKGROUND: Actinic keratoses (AKs) are dysplastic lesions of the epidermis that have the potential to progress to non-melanoma skin cancers (NMSC). Traditional photodynamic therapy (PDT) requires a pre-illumination incubation time, which adds to overall in-office time and has been linked to pain. Our group has found a novel protocol to effectively treat AKs with PDT that eliminates the pre-illumination incubation period and uses 2 back-to-back cycles of 16 minute 40 seconds.

METHODS: The patient was prepped with soapy water and isopropyl alcohol, and thick AKs were descaled with a curette. Next, 5-aminolevulinic acid (ALA) was applied to the treatment areas and the patient was immediately placed under the blue light for 33 minutes and 20 seconds (two cycles of 16m/40s).

RESULTS: During therapy, the patient reported no pain. At one week, treated areas revealed a good reaction. The procedure was repeated at one month to treat residual AKs. At a 4-month follow-up, the patient's face and scalp showed near clearance of any AKs.

CONCLUSION: During PDT, the photosensitizer aminolevulinic acid (ALA), or in Europe methyl aminolevulinate (MAL), is utilized as a synthetic precursor that preferentially accumulates in dysplastic cells. The precursor then converts to PpIX via the heme pathway and causes apoptosis of the cells when excited, most commonly by either blue-violet (400-430 nm) or red (630-635 nm) light. Shorter incubation times are associated with reduced pain because less PpIX will have accumulated in the treated tissue by the start of the exposure to the light. The doubling of the light exposure time allows comparable levels of the photosensitizing molecule to accumulate and be activated so as to produce an equivalent reaction. The associated reduction in pain along with a more convenient treatment schedule makes this PDT protocol more tolerable and convenient to some patients.

J Drugs Dermatol. 2017;16(3):275-278.

Aminolevulinic Acid Topical

MedlinePlus

... in combination with photodynamic therapy (PDT; special blue light) to treat actinic keratoses (small crusty or scaly ... photosensitizing agents. When aminolevulinic acid is activated by light, it damages the cells of actinic keratosis lesions.

Actin Polymerization is Stimulated by Actin Crosslinking Protein Palladin

PubMed Central

Gurung, Ritu; Yadav, Rahul; Brungardt, Joseph G.; Orlova, Albina; Egelman, Edward H.; Beck, Moriah R.

2016-01-01

The actin scaffold protein palladin regulates both normal cell migration and invasive cell motility, processes that require the coordinated regulation of actin dynamics. However, the potential effect of palladin on actin dynamics has remained elusive. Here we show that the actin binding immunoglobulin-like domain of palladin, which is directly responsible for both actin binding and bundling, also stimulates actin polymerization in vitro. Palladin eliminated the lag phase that is characteristic of the slow nucleation step of actin polymerization. Furthermore, palladin dramatically reduced depolymerization, slightly enhanced the elongation rate, and did not alter the critical concentration. Microscopy and in vitro crosslinking assays reveal differences in actin bundle architecture when palladin is incubated with actin before or after polymerization. These results suggest a model whereby palladin stimulates a polymerization-competent form of G-actin, akin to metal ions, either through charge neutralization or conformational changes. PMID:26607837

Randomized Vehicle-Controlled Study of Short Drug Incubation Aminolevulinic Acid Photodynamic Therapy for Actinic Keratoses of the Face or Scalp.

PubMed

Pariser, David M; Houlihan, Anna; Ferdon, Mary Beth; Berg, James E

2016-03-01

Aminolevulinic acid photodynamic therapy (ALA-PDT) can be effective and well tolerated when applied over a broad area and for short drug incubation times. To evaluate the effect of short-incubation time and application method on the safety and efficacy of ALA-PDT versus vehicle (VEH-PDT) in the treatment of actinic keratoses (AKs) of the face or scalp. Aminolevulinic acid or VEH was applied to face or scalp as a broad area application for 1, 2, or 3 hours or as a spot application for 2 hours before blue light activation. An identical treatment was repeated at Week 8 if any AK lesions remained. Median AK clearance rate for ALA-treated subjects ranged from 68% to 79% at Week 12, compared with 7% of the VEH-treated group (p < .0001). Complete clearance rate for ALA-treated subjects ranged from 17% (8/46) to 30% (14/47) at Week 12, compared with 2% (1/46) of the VEH-treated group (p = .0041). The safety profile seen in this study is consistent with previously reported side effects of the therapy. Short-incubation ALA-PDT was found to be superior to VEH-PDT for AK lesion clearance. A second treatment improves efficacy.

Keratosis reduces sensitivity of anal cytology in detecting anal intraepithelial neoplasia.

PubMed

ElNaggar, Adam C; Santoso, Joseph T; Xie, Huiwen Bill

2012-02-01

To identify factors that may contribute to poor sensitivity of anal cytology in contrast to the sensitivity of anoscopy in heterosexual women. We analyzed 324 patients with biopsy confirmed diagnosis of genital intraepithelial neoplasia (either vulva, vaginal, or cervical) from 2006 to 2011 who underwent both anal cytology and anoscopy. Cytology, anoscopy, and biopsy results were recorded. Biopsy specimens underwent independent analysis for quality of specimen. Also, biopsy specimens were analyzed for characteristics that may contribute to correlation, or lack thereof, between anal cytology and anoscopic directed biopsy. 133 (41%) patients had abnormal anoscopy and underwent directed biopsy. 120 patients with normal anal cytology had anoscopy directed biopsies, resulting in 58 cases of AIN (sensitivity 9.4%; 0.039-0.199). This cohort was noted to have extensive keratosis covering the entire dysplastic anal lesion. 18 patients yielded abnormal anal cytology. Of these patients, 13 had anoscopic directed biopsies revealing 6 with AIN and absent keratosis (specificity 88.6%; 0.78-0.95). The κ statistic for anal cytology and anoscopy was -0.0213 (95% CI=-0.128-0.086). Keratosis reduces the sensitivity of anal cytology. Furthermore, anal cytology poorly correlates with anoscopy in the detection of AIN (κ statistic=-0.0213). Copyright © 2011 Elsevier Inc. All rights reserved.

Actin Interacting Protein1 and Actin Depolymerizing Factor Drive Rapid Actin Dynamics in Physcomitrella patens[W

PubMed Central

Augustine, Robert C.; Pattavina, Kelli A.; Tüzel, Erkan; Vidali, Luis; Bezanilla, Magdalena

2011-01-01

The remodeling of actin networks is required for a variety of cellular processes in eukaryotes. In plants, several actin binding proteins have been implicated in remodeling cortical actin filaments (F-actin). However, the extent to which these proteins support F-actin dynamics in planta has not been tested. Using reverse genetics, complementation analyses, and cell biological approaches, we assessed the in vivo function of two actin turnover proteins: actin interacting protein1 (AIP1) and actin depolymerizing factor (ADF). We report that AIP1 is a single-copy gene in the moss Physcomitrella patens. AIP1 knockout plants are viable but have reduced expansion of tip-growing cells. AIP1 is diffusely cytosolic and functions in a common genetic pathway with ADF to promote tip growth. Specifically, ADF can partially compensate for loss of AIP1, and AIP1 requires ADF for function. Consistent with a role in actin remodeling, AIP1 knockout lines accumulate F-actin bundles, have fewer dynamic ends, and have reduced severing frequency. Importantly, we demonstrate that AIP1 promotes and ADF is essential for cortical F-actin dynamics. PMID:22003077

Control of actin-based motility through localized actin binding

PubMed Central

Banigan, Edward J.; Lee, Kun-Chun; Liu, Andrea J.

2014-01-01

A wide variety of cell biological and biomimetic systems use actin polymerization to drive motility. It has been suggested that an object such as a bacterium can propel itself by self-assembling a high concentration of actin behind it if it is repelled by actin. However, it is also known that it is essential for the moving object to bind actin. Therefore, a key question is how the actin tail can propel an object when it both binds and repels the object. We present a physically consistent Brownian dynamics model for actin-based motility that includes the minimal components of the dendritic nucleation model and allows for both attractive and repulsive interactions between actin and a moveable disk. We find that the concentration gradient of filamentous actin generated by polymerization is sufficient to propel the object, even with moderately strong binding interactions. Additionally, actin binding can act as a biophysical cap, and may directly control motility through modulation of network growth. Overall, this mechanism is robust in that it can drive motility against a load up to a stall pressure that depends on the Young’s modulus of the actin network and can explain several aspects of actin-based motility. PMID:24225232

46 CFR 7.150 - Canadian (BC) and United States (AK) Borders to Cape Spencer, AK.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 1 2013-10-01 2013-10-01 false Canadian (BC) and United States (AK) Borders to Cape Spencer, AK. 7.150 Section 7.150 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.150 Canadian (BC) and United States (AK) Borders to Cape...

46 CFR 7.150 - Canadian (BC) and United States (AK) Borders to Cape Spencer, AK.

Code of Federal Regulations, 2010 CFR

2010-10-01

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46 CFR 7.150 - Canadian (BC) and United States (AK) Borders to Cape Spencer, AK.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 1 2014-10-01 2014-10-01 false Canadian (BC) and United States (AK) Borders to Cape Spencer, AK. 7.150 Section 7.150 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.150 Canadian (BC) and United States (AK) Borders to Cape...

46 CFR 7.150 - Canadian (BC) and United States (AK) Borders to Cape Spencer, AK.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Canadian (BC) and United States (AK) Borders to Cape Spencer, AK. 7.150 Section 7.150 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.150 Canadian (BC) and United States (AK) Borders to Cape...

46 CFR 7.150 - Canadian (BC) and United States (AK) Borders to Cape Spencer, AK.

Code of Federal Regulations, 2012 CFR

2012-10-01

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Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy

PubMed Central

Cunningham, Trevor J.; Tabacchi, Mary; Eliane, Jean-Pierre; Tuchayi, Sara Moradi; Manivasagam, Sindhu; Mirzaalian, Hengameh; Turkoz, Ahu; Kopan, Raphael; Schaffer, Andras; Saavedra, Arturo P.; Wallendorf, Michael; Cornelius, Lynn A.; Demehri, Shadmehr

2016-01-01

BACKGROUND. Actinic keratosis is a precursor to cutaneous squamous cell carcinoma. Long treatment durations and severe side effects have limited the efficacy of current actinic keratosis treatments. Thymic stromal lymphopoietin (TSLP) is an epithelium-derived cytokine that induces a robust antitumor immunity in barrier-defective skin. Here, we investigated the efficacy of calcipotriol, a topical TSLP inducer, in combination with 5-fluorouracil (5-FU) as an immunotherapy for actinic keratosis. METHODS. The mechanism of calcipotriol action against skin carcinogenesis was examined in genetically engineered mouse models. The efficacy and safety of 0.005% calcipotriol ointment combined with 5% 5-FU cream were compared with Vaseline plus 5-FU for the field treatment of actinic keratosis in a randomized, double-blind clinical trial involving 131 participants. The assigned treatment was self-applied to the entirety of the qualified anatomical sites (face, scalp, and upper extremities) twice daily for 4 consecutive days. The percentage of reduction in the number of actinic keratoses (primary outcome), local skin reactions, and immune activation parameters were assessed. RESULTS. Calcipotriol suppressed skin cancer development in mice in a TSLP-dependent manner. Four-day application of calcipotriol plus 5-FU versus Vaseline plus 5-FU led to an 87.8% versus 26.3% mean reduction in the number of actinic keratoses in participants (P < 0.0001). Importantly, calcipotriol plus 5-FU treatment induced TSLP, HLA class II, and natural killer cell group 2D (NKG2D) ligand expression in the lesional keratinocytes associated with a marked CD4+ T cell infiltration, which peaked on days 10–11 after treatment, without pain, crusting, or ulceration. CONCLUSION. Our findings demonstrate the synergistic effects of calcipotriol and 5-FU treatment in optimally activating a CD4+ T cell–mediated immunity against actinic keratoses and, potentially, cancers of the skin and other organs. TRIAL

Photodynamic therapy of nonmelanoma skin cancer with topical hypericum perforatum extract--a pilot study.

PubMed

Kacerovská, Denisa; Pizinger, Karel; Majer, Filip; Smíd, Frantisek

2008-01-01

Hypericin, the photoactive compound of Hypericum perforatum, is probably the most powerful photosensitizer found in nature. This compound has shown high potency in the photodynamic treatment of tumor cells. However, there is only limited knowledge regarding the photodynamic effect of hypericin on nonmelanoma skin cancer cells. The aim of this prospective study was to investigate the efficacy of photodynamic therapy with topical application of an extract of H. perforatum in actinic keratosis, basal cell carcinoma (BCC) and morbus Bowen (carcinoma in situ). The study was carried out on 34 patients--eight with actinic keratoses (AKs), 21 with BCC and five with Bowen's disease. The extract of H. perforatum was applied on the skin lesions under occlusion and that was followed by irradiation with 75 J cm(-2) of red light 2 h later. The treatment was performed weekly for 6 weeks on average. The percentage of complete clinical response was 50% for AKs, 28% in patients with superficial BCC and 40% in patients with Bowen's disease. There was only a partial remission seen in patients with nodular BCCs. A complete disappearance of tumor cells was found in the histologic preparation of 11% of patients with superficial BCCs and 80% in the patients with Bowen's disease. All patients complained of burning and pain sensations during irradiation. Although the results of this first clinical trial could be regarded as disappointing, there are still possibilities for improvement. Better preparation of the lesions, enhancement of hypericin delivery and other types of light exposure procedures could significantly improve the clinical outcomes of this relatively inexpensive treatment modality.

Inverted follicular keratosis: dermoscopic and reflectance confocal microscopic features.

PubMed

Armengot-Carbo, M; Abrego, A; Gonzalez, T; Alarcon, I; Alos, L; Carrera, C; Malvehy, J; Puig, S

2013-01-01

Inverted follicular keratosis (IFK) is a rare benign tumor which usually appears as a firm papule on the face. The diagnosis is generally made by histopathology because the clinical appearance is difficult to differentiate from other lesions. Dermoscopic features of IFK have not been established to date. Herein we describe the dermoscopic findings of 4 cases of IFK. Radial peripheral hairpin vessels surrounded by a whitish halo arranged around a central white-yellowish amorphous area were observed in 3 cases, and glomerular vessels were present in the central area of one of them. The fourth case also presented a central white amorphous area but showed arborizing vessels. Reflectance confocal microscopy (available in 1 case) revealed a broadened honeycomb pattern, epidermal projections and hairpin and glomerular vessels. To our knowledge this is the first case series describing the dermoscopic features of inverted follicular keratosis and the first confocal microscopy description of this entity.

Actin Bodies in Yeast Quiescent Cells: An Immediately Available Actin Reserve?

PubMed Central

Pinson, Benoît; Salin, Bénédicte; Daignan-Fornier, Bertrand

2006-01-01

Most eukaryotic cells spend most of their life in a quiescent state, poised to respond to specific signals to proliferate. In Saccharomyces cerevisiae, entry into and exit from quiescence are dependent only on the availability of nutrients in the environment. The transition from quiescence to proliferation requires not only drastic metabolic changes but also a complete remodeling of various cellular structures. Here, we describe an actin cytoskeleton organization specific of the yeast quiescent state. When cells cease to divide, actin is reorganized into structures that we named “actin bodies.” We show that actin bodies contain F-actin and several actin-binding proteins such as fimbrin and capping protein. Furthermore, by contrast to actin patches or cables, actin bodies are mostly immobile, and we could not detect any actin filament turnover. Finally, we show that upon cells refeeding, actin bodies rapidly disappear and actin cables and patches can be assembled in the absence of de novo protein synthesis. This led us to propose that actin bodies are a reserve of actin that can be immediately mobilized for actin cables and patches formation upon reentry into a proliferation cycle. PMID:16914523

The association between osteoporotic hip fractures and actinic lesions as a biomarker for cumulative sun exposure in older people-a retrospective case-control study in Argentina.

PubMed

Perroud, H A; Dagatti, M S; Amigot, B; Levit, G P; Tomat, M F; Morosano, M E; Masoni, A M; Pezzotto, S M

2017-05-01

The aim of this study was to analyze the association between the presence of actinic lesions (solar keratosis and non-melanoma skin cancer) and osteoporotic hip fractures in older patients. Both pathologies are common conditions in this age group. Since cumulative sun exposure is difficult to quantify, the presence of actinic lesions can be used to indirectly analyze the association between ultraviolet radiation and osteoporotic hip fractures. This was an observational case-control study. We reviewed the centralized medical records of patients with hip fracture (cases, n = 51) and patients with other diseases hospitalized in the same institution and period (controls, n = 59). The mean age of the patients was 80 ± 8.3 years (range 50-103 years). Differences in maternal hip fracture history were found between cases and controls (14.8 and 8 %, respectively; p = 0.047). Falls history in the past year was higher in cases than in controls (p < 0.0001). Actinic lesions were observed in 32.7 % of patients (prevalence rate 23.5 % in cases, 40.7 % in controls; p = 0.04). When considering patients with actinic lesions, controls have a higher FRAX score compared with cases. Although sun exposure is recommended for bone health, it represents a risk factor for actinic lesions. The presence of actinic lesions may indicate a lower osteoporotic hip fracture risk. A balance between adequate lifetime sun exposure and protection against its adverse effects is required for each patient, in the context of geographic location.

Epidemiology of skin diseases in renal transplant recipients in a tertiary hospital.

PubMed

Chen, Qi Ping; Aw, Derrick C W

2010-12-01

There is no published epidemiological data on skin diseases in kidney transplant recipients in this tropical country, which has multi-ethnic groups with the Chinese as the predominant ethnic group. Skin diseases of 143 renal transplant recipients were studied in a skin clinic of a tertiary institution during annual surveillance visits from June 2006 to March 2009. Our study showed that except the common drug specific skin manifestations, sebaceous hyperplasia (56.6%), seborrheic keratosis (60.8%), melanocytic naevi (76.9%), skin tags (37.1%) and viral (29.4%) and fungal (20.3%) infections were the most prevalent skin diseases among renal transplant recipients living in Singapore. The prevalence of pre-malignant and malignant tumours was very low (11.2% actinic keratosis, 1.4% Bowen's disease, 1.4% squamous cell carcinoma, 0.7% basal cell carcinoma, 0.7% keratoacanthoma). Male predominance was seen in sebaceous hyperplasia (72.4% vs 32.1%), actinic keratosis (17.2% vs 1.8%), viral (36.8% vs 19.6%) and fungal (27.6% vs 8.9%) infections. Our study also showed increased prevalence of sebaceous hyperplasia with increased age but its prevalence was significantly higher than that reported in the age matched general population. The prevalence of seborrheic keratosis, actinic keratosis and viral infection correlated positively with post-transplant duration. Our study provides epidemiological data for the prevalence of skin diseases in renal transplant recipients. It emphasises the importance of dermatologic follow-up for renal transplant patients in order to obtain a diagnosis and manage treatable skin diseases.

P16 UV mutations in human skin epithelial tumors.

PubMed

Soufir, N; Molès, J P; Vilmer, C; Moch, C; Verola, O; Rivet, J; Tesniere, A; Dubertret, L; Basset-Seguin, N

1999-09-23

The p16 gene expresses two alternative transcripts (p16alpha and p16beta) involved in tumor suppression via the retinoblastoma (Rb) or p53 pathways. Disruption of these pathways can occur through inactivation of p16 or p53, or activating mutations of cyclin dependant kinase 4 gene (Cdk4). We searched for p16, Cdk4 and p53 gene mutations in 20 squamous cell carcinomas (SSCs), 1 actinic keratosis (AK), and 28 basal cell carcinomas (BCCs), using PCR-SSCP. A deletion and methylation analysis of p16 was also performed. Six different mutations (12%) were detected in exon 2 of p16 (common to p16alpha and p16beta), in five out of 21 squamous lesions (24%) (one AK and four SCCs) and one out of 28 BCCs (3.5%). These included four (66%) ultraviolet (UV)-type mutations (two tandems CC : GG to TT : AA transitions and two C : G to T : A transitions at dipyrimidic site) and two transversions. P53 mutations were present in 18 samples (37%), mostly of UV type. Of these, only two (one BCC and one AK) harboured simultaneously mutations of p16, but with no consequence on p16beta transcript. Our data demonstrate for the first time the presence of p16 UV induced mutations in non melanoma skin cancer, particularly in the most aggressive SCC type, and support that p16 and p53 are involved in two independent pathways in skin carcinogenesis.

Claudins 1, 2, 3, 4, 5 and 7 in solar keratosis and squamocellular carcinoma of the skin

PubMed Central

Hintsala, Hanna-Riikka; Siponen, Maria; Haapasaari, Kirsi-Maria; Karihtala, Peeter; Soini, Ylermi

2013-01-01

Claudins are tight junction proteins regulating the paracellular permeability of cell layers. We investigated the expression of claudins 1, 2, 3, 4, 5 and 7 in a sample set consisting of a total of 93 cases representing normal skin, actinic keratoses and squamous cell carcinomas of the skin. There were several changes found in claudin expression. Claudin 1 appeared to be progressively decreased in solar keratosis and skin squamous cell carcinomas compared to normal skin while expression of claudin 2 was increased. With claudins 3 and 5 occasional immunoreactivity was found in squamous cell carcinomas. Claudins 4 and 7 were variably expressed in skin neoplasia compared to normal skin. According to the results expression of claudins 1 and 2 change in parallel with the severity of the epidermal preneoplastic and neoplastic lesions thus probably influencing the disturbed epithelial polarity characteristic of these lesions. Claudin 1 under- and claudin 2 overexpression also lead to a leakier epithelial barrier function of the skin with a resulting damage to skin epithelial resistance. Other claudins investigated in this study did not show progressive changes even though occasional overexpression of them was found in skin squamous cell carcinoma. PMID:24294371

Potential Role of S100A8 in Cutaneous Squamous Cell Carcinoma Differentiation.

PubMed

Shin, Jung-Min; Chang, In-Kyu; Lee, Young-Ho; Yeo, Min-Kyung; Kim, Jin-Man; Sohn, Kyung-Cheol; Im, Myung; Seo, Young-Joon; Kim, Chang-Deok; Lee, Jeung-Hoon; Lee, Young

2016-04-01

S100A8 is differentially expressed in various cell types and is associated with a number of malignant disorders. S100A8 may affect tumor biology. However, its role in cutaneous squamous cell carcinoma (SCC) is not well established. This study aims to investigate the relationship between S100A8 and cutaneous SCC development. We performed immunohistochemical staining to detect S100A8 expression in facial skin specimens of premalignant actinic keratosis (AK), malignant SCC, and normal tissues. In addition, we utilized postconfluence and high calcium-induced differentiation in a culture system model. Furthermore, we constructed a recombinant adenovirus expressing GFP-tagged S100A8 to investigate the role of S100A8 in SCC cell differentiation. S100A8 was significantly overexpressed in human cutaneous SCC compared to that in normal and AK tissues. S100A8 was gradually upregulated in SCC cells in a post-confluence-induced differentiation model. Overexpression of S100A8 in SCC cells induced by adenoviral transduction led to increased expression levels of differentiation markers, such as loricrin, involucrin, and filaggrin. S100A8 overexpression also increased loricrin and involucrin luciferase activity. S100A8 regulates cutaneous SCC differentiation and induces well-differentiated SCC formation in skin.

Glycophenotype evaluation in cutaneous tumors using lectins labeled with acridinium ester.

PubMed

Lima, Luiza Rayanna Amorim; Bezerra, Matheus Filgueira; Almeida, Sinara Mônica Vitalino; Silva, Lúcia Patrícia Bezerra Gomes; Beltrão, Eduardo Isidoro Carneiro; Carvalho Júnior, Luiz Bezerra

2013-01-01

Tumor cells show alterations in their glycosylation patterns when compared to normal cells. Lectins can be used to evaluate these glycocode changes. Chemiluminescence assay is an effective technique for quantitative analysis of proteins, nucleic acids, and carbohydrates due to its high sensitivity, specificity, and rapid testing. To use histochemiluminescence based on lectin conjugated to acridinium ester (AE) for the investigation of glycophenotype changes in cutaneous tumors. Concanavalin A (Con A), Peanut agglutinin (PNA), Ulex europaeus agglutinin-I (UEA-I), and Maackia amurensis agglutinin (MAA) were conjugated to acridinium ester. Biopsies of cutaneous tumors and normal skin were incubated with the lectins-AE, and chemiluminescence was quantified and expressed as Relative Light Units (RLU). Results. Actinic keratosis (AK), keratoacanthoma (KA), squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) showed lower expression of α -D-glucose/mannose and α -L-fucose residues compared to normal tissue. Cutaneous tumors displayed higher expression of Gal- β (1-3)-GalNAc residues than normal tissue. AK and SCC exhibited higher expression of Neu5Ac- α (2,3)Gal residues than normal epidermis. KA and BCC showed equivalent RLU values compared to normal tissue. Lectin histochemiluminescence allowed quantitative assessment of the carbohydrate expression in cutaneous tissues, contributing to eliminate the subjectivity of conventional techniques used in the histopathological diagnosis.

Technical advance: identification of plant actin-binding proteins by F-actin affinity chromatography

NASA Technical Reports Server (NTRS)

Hu, S.; Brady, S. R.; Kovar, D. R.; Staiger, C. J.; Clark, G. B.; Roux, S. J.; Muday, G. K.

2000-01-01

Proteins that interact with the actin cytoskeleton often modulate the dynamics or organization of the cytoskeleton or use the cytoskeleton to control their localization. In plants, very few actin-binding proteins have been identified and most are thought to modulate cytoskeleton function. To identify actin-binding proteins that are unique to plants, the development of new biochemical procedures will be critical. Affinity columns using actin monomers (globular actin, G-actin) or actin filaments (filamentous actin, F-actin) have been used to identify actin-binding proteins from a wide variety of organisms. Monomeric actin from zucchini (Cucurbita pepo L.) hypocotyl tissue was purified to electrophoretic homogeneity and shown to be native and competent for polymerization to actin filaments. G-actin, F-actin and bovine serum albumin affinity columns were prepared and used to separate samples enriched in either soluble or membrane-associated actin-binding proteins. Extracts of soluble actin-binding proteins yield distinct patterns when eluted from the G-actin and F-actin columns, respectively, leading to the identification of a putative F-actin-binding protein of approximately 40 kDa. When plasma membrane-associated proteins were applied to these columns, two abundant polypeptides eluted selectively from the F-actin column and cross-reacted with antiserum against pea annexins. Additionally, a protein that binds auxin transport inhibitors, the naphthylphthalamic acid binding protein, which has been previously suggested to associate with the actin cytoskeleton, was eluted in a single peak from the F-actin column. These experiments provide a new approach that may help to identify novel actin-binding proteins from plants.

Technical advance: identification of plant actin-binding proteins by F-actin affinity chromatography.

PubMed

Hu, S; Brady, S R; Kovar, D R; Staiger, C J; Clark, G B; Roux, S J; Muday, G K

2000-10-01

Proteins that interact with the actin cytoskeleton often modulate the dynamics or organization of the cytoskeleton or use the cytoskeleton to control their localization. In plants, very few actin-binding proteins have been identified and most are thought to modulate cytoskeleton function. To identify actin-binding proteins that are unique to plants, the development of new biochemical procedures will be critical. Affinity columns using actin monomers (globular actin, G-actin) or actin filaments (filamentous actin, F-actin) have been used to identify actin-binding proteins from a wide variety of organisms. Monomeric actin from zucchini (Cucurbita pepo L.) hypocotyl tissue was purified to electrophoretic homogeneity and shown to be native and competent for polymerization to actin filaments. G-actin, F-actin and bovine serum albumin affinity columns were prepared and used to separate samples enriched in either soluble or membrane-associated actin-binding proteins. Extracts of soluble actin-binding proteins yield distinct patterns when eluted from the G-actin and F-actin columns, respectively, leading to the identification of a putative F-actin-binding protein of approximately 40 kDa. When plasma membrane-associated proteins were applied to these columns, two abundant polypeptides eluted selectively from the F-actin column and cross-reacted with antiserum against pea annexins. Additionally, a protein that binds auxin transport inhibitors, the naphthylphthalamic acid binding protein, which has been previously suggested to associate with the actin cytoskeleton, was eluted in a single peak from the F-actin column. These experiments provide a new approach that may help to identify novel actin-binding proteins from plants.

Topical Colchicine Gel versus Diclofenac Sodium Gel for the Treatment of Actinic Keratoses: A Randomized, Double-Blind Study.

PubMed

Faghihi, Gita; Elahipoor, Azam; Iraji, Fariba; Behfar, Shadi; Abtahi-Naeini, Bahareh

2016-01-01

Introduction. Actinic keratoses (AKs), a premalignant skin lesion, are a common lesion in fair skin. Although destructive treatment remains the gold standard for AKs, medical therapies may be preferable due to the comfort and reliability .This study aims to compare the effects of topical 1% colchicine gel and 3% diclofenac sodium gel in AKs. Materials and Methods. In this randomized double-blind study, 70 lesions were selected. Patients were randomized before receiving either 1% colchicine gel or 3% diclofenac sodium cream twice a day for 6 weeks. Patients were evaluated in terms of their lesion size, treatment complications, and recurrence at 7, 30, 60, and 120 days after treatment. Results. The mean of changes in the size was significant in both groups both before and after treatment (<0.001). The mean lesion size before treatment and at 30, 60, and 120 days was not different between the two groups (p > 0.05). No case of erythema was seen in the colchicine group, while erythema was seen in 22.9% (eight cases) of patients in the diclofenac sodium group (p = 0.005). Conclusions. 1% colchicine gel was a safe and effective medication with fewer side effects and lack of recurrence of the lesion.

Steady-state nuclear actin levels are determined by export competent actin pool.

PubMed

Skarp, Kari-Pekka; Huet, Guillaume; Vartiainen, Maria K

2013-10-01

A number of studies in the last decade have irrevocably promoted actin into a fully fledged member of the nuclear compartment, where it, among other crucial tasks, facilitates transcription and chromatin remodeling. Changes in nuclear actin levels have been linked to different cellular processes: decreased nuclear actin to quiescence and increased nuclear actin to differentiation. Importin 9 and exportin 6 transport factors are responsible for the continuous nucleocytoplasmic shuttling of actin, but the mechanisms, which result in modulated actin levels, have not been characterized. We find that in cells growing under normal growth conditions, the levels of nuclear actin vary considerably from cell to cell. To understand the basis for this, we have extensively quantified several cellular parameters while at the same time recording the import and export rates of green fluorescent protein (GFP)-tagged actin. Surprisingly, our dataset shows that the ratio of nuclear to cytoplasmic fluorescence intensity, but not nuclear shape, size, cytoplasm size, or their ratio, correlates negatively with both import and export rate of actin. This suggests that high-nuclear actin content is maintained by both diminished import and export. The high nuclear actin containing cells still show high mobility of actin, but it is not export competent, suggesting increased binding of actin to nuclear complexes. Creation of such export incompetent actin pool would ensure enough actin is retained in the nucleus and make it available for the various nuclear functions described for actin. Copyright © 2013 Wiley Periodicals, Inc.

Lights, camera, actin.

PubMed

Rubenstein, Peter A; Wen, Kuo-Kuang

2005-10-01

Actin participates in many important biological processes. Currently, intensive investigation is being carried out in a number of laboratories concerning the function of actin in these processes and the molecular basis of its functions. We present a glimpse into four of these areas: actin-like proteins in bacterial cells, actin in the eukaryotic nucleus, the conformational plasticity of the actin filament, and finally, Arp2/3-dependent regulation of actin filament branching and creation of new filament barbed ends. IUBMB Life, 57: 683-687, 2005.

Treatment Options for Actinic Keratosis

MedlinePlus

... of skin biopsies: Shave biopsy : A sterile razor blade is used to “shave-off” the abnormal-looking ... the surface of the skin with a small blade. Electrodesiccation and curettage : The tumor is cut from ...

Actin-binding proteins sensitively mediate F-actin bundle stiffness

NASA Astrophysics Data System (ADS)

Claessens, Mireille M. A. E.; Bathe, Mark; Frey, Erwin; Bausch, Andreas R.

2006-09-01

Bundles of filamentous actin (F-actin) form primary structural components of a broad range of cytoskeletal processes including filopodia, sensory hair cell bristles and microvilli. Actin-binding proteins (ABPs) allow the cell to tailor the dimensions and mechanical properties of the bundles to suit specific biological functions. Therefore, it is important to obtain quantitative knowledge on the effect of ABPs on the mechanical properties of F-actin bundles. Here we measure the bending stiffness of F-actin bundles crosslinked by three ABPs that are ubiquitous in eukaryotes. We observe distinct regimes of bundle bending stiffness that differ by orders of magnitude depending on ABP type, concentration and bundle size. The behaviour observed experimentally is reproduced quantitatively by a molecular-based mechanical model in which ABP shearing competes with F-actin extension/compression. Our results shed new light on the biomechanical function of ABPs and demonstrate how single-molecule properties determine mesoscopic behaviour. The bending mechanics of F-actin fibre bundles are general and have implications for cytoskeletal mechanics and for the rational design of functional materials.

Association of atopy and tentative diagnosis of skin cancer - results from occupational skin cancer screenings.

PubMed

Schäfer, I; Mohr, P; Zander, N; Fölster-Holst, R; Augustin, M

2017-12-01

The relationship between atopic conditions and carcinoma of the skin has been described inconsistently. Population-based data providing information on atopic diseases as well as on skin cancer are sparse. To determine the correlation between atopy and prevalence of precanceroses, non-melanoma skin cancer and malignant melanoma (MM), while taking into account known risk factors for skin cancer. Data from occupational skin cancer screenings were analysed in a cross-sectional study. Dermatologists performed whole body examinations and collected medical histories. Subjects comprised all employees (16-70 years) examined from 2006 to 2014. 'Atopy' was defined by clinical screening diagnosis and/or by participant-reported, pre-existing atopic dermatitis, allergic asthma or other specified allergies confirmed by a physician. Tentative screening diagnoses of skin cancer related to actinic keratosis, basal cell carcinoma and malignant melanoma. The study cohort comprised 90 265 employees (mean age 43 ± 11 years, 58.5% male), 30.7% of whom were ever diagnosed with an atopic disease. Persons with atopic conditions recorded in their medical history and at the time of screening had a significantly lower prevalence of actinic keratosis (AK), basal cell carcinoma (BCC) and MM. After controlling for age, sex and relevant risk factors (skin type, childhood sun burns), atopy remained significantly protective against BCC (OR 0.77) and MM (OR 0.53). Design limitations of the study include that all findings of skin cancer were based on clinical examination only and must therefore be considered tentative diagnoses. Furthermore, owing to the cross-sectional study design, causal pathways cannot be proven. However, analyses of data from such a large and general population-based cohort afford valuable insights into the relationship between atopic diseases and skin cancer. They provide the grounds for prospective cohort studies to evaluate and dissect the underlying mechanism. © 2017

Two-Step Irradiance Treatment Can Achieve Excellent Pain Control During Red Light 5-Aminolevulinic Acid Photodynamic Therapy for Actinic Keratoses.

PubMed

Paragh, Gyorgy; Zeitouni, Nathalie C

2018-03-01

To evaluate the ability of two-step irradiance to maintain pain control during red light 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) for actinic keratoses (AK) and assess factors influencing pain. PDT provides excellent clinical and cosmetic results in the treatment AK and early basal cell carcinomas (BCC). Widespread use of PDT is limited, in part, by pain. A two-step irradiance method for PDT has previously been shown to significantly reduce PDT-associated pain during the treatment of BCC, but the ability of this method to limit pain during the treatment of AKs has not been reported. We performed a retrospective chart review to assess the level of pain during AK treatment by red light PDT (n = 99). Natural density filter was used to reduce the irradiance of the light source and initially 10 J/cm 2 dose was delivered at 35 mW/cm 2 and then, 65 J/cm 2 dose was delivered at 70 mW/cm 2 . Pain level was measured using a 10-point visual analog scale at three points during the procedure. Pain was low to moderate in most patients (mean ± standard error of the mean pain score: 2.35 ± 0.19). Higher pain was seen midprocedure versus at the beginning (p < 0.0001) and at the end (p = 0.003) of PDT. There was no significant difference in pain perception between genders and different treatment areas. Our results provide evidence that red light ALA PDT of AKs is very well tolerated with the two-step irradiance protocol.

Nuclear Functions of Actin

PubMed Central

Visa, Neus; Percipalle, Piergiorgio

2010-01-01

Actin participates in several essential processes in the cell nucleus. Even though the presence of actin in the nucleus was proposed more than 30 years ago, nuclear processes that require actin have been only recently identified. Actin is part of chromatin remodeling complexes; it is associated with the transcription machineries; it becomes incorporated into newly synthesized ribonucleoproteins; and it influences long-range chromatin organization. As in the cytoplasm, nuclear actin works in conjunction with different types of actin-binding proteins that regulate actin function and bridge interactions between actin and other nuclear components. PMID:20452941

How actin network dynamics control the onset of actin-based motility

PubMed Central

Kawska, Agnieszka; Carvalho, Kévin; Manzi, John; Boujemaa-Paterski, Rajaa; Blanchoin, Laurent; Martiel, Jean-Louis; Sykes, Cécile

2012-01-01

Cells use their dynamic actin network to control their mechanics and motility. These networks are made of branched actin filaments generated by the Arp2/3 complex. Here we study under which conditions the microscopic organization of branched actin networks builds up a sufficient stress to trigger sustained motility. In our experimental setup, dynamic actin networks or “gels” are grown on a hard bead in a controlled minimal protein system containing actin monomers, profilin, the Arp2/3 complex and capping protein. We vary protein concentrations and follow experimentally and through simulations the shape and mechanical properties of the actin gel growing around beads. Actin gel morphology is controlled by elementary steps including “primer” contact, growth of the network, entanglement, mechanical interaction and force production. We show that varying the biochemical orchestration of these steps can lead to the loss of network cohesion and the lack of effective force production. We propose a predictive phase diagram of actin gel fate as a function of protein concentrations. This work unveils how, in growing actin networks, a tight biochemical and physical coupling smoothens initial primer-caused heterogeneities and governs force buildup and cell motility. PMID:22908255

Alveolar ridge keratosis - a retrospective clinicopathological study

PubMed Central

2013-01-01

Background Alveolar ridge keratosis (ARK) is a distinct, benign clinicopathological entity, characterized by a hyperkeratotic plaque or patch that occurs on the alveolar edentulous ridge or on the retromolar trigone, considered to be caused by chronic frictional trauma. The aim of this retrospective study is to present the clinicopathological features of 23 consecutive cases of ARK. Material and methods The 23 biopsy samples of ARK were selected and pathological features were revised (keratosis, acanthosis, surface architecture, and inflammation). Factors such as the patient’s gender, age, anatomical location, tobacco and alcohol use were analyzed. Results Sixteen out of the 23 cases studied were men and 7 women with a mean age of 55.05 (age ranged from 17 to 88 years). Thirteen cases had a history of tobacco habit, amongst whom, 4 also presented alcohol consumption. All the cases presented only unilateral lesions. Nineteen cases involved the retromolar trigone while 4 cases involved edentulous alveolar ridges. When observed microscopically, the lesions were mainly characterized by moderate to important hyperorthokeratosis. Inflammation was scanty or absent. In four of the cases, the presence of melanin pigment in the superficial corium or in the cytoplasm of macrophages was detected. None of the cases showed any features of dysplasia. Conclusion Our results reveal that ARK is a benign lesion. However, the high prevalence of smokers amongst the patients might suggest that some potentially malignant disorders such as tobacco associated leukoplakia may clinically mimic ARK. PMID:23587097

Alveolar ridge keratosis--a retrospective clinicopathological study.

PubMed

Bellato, Lorenzo; Martinelli-Kläy, Carla P; Martinelli, Celso R; Lombardi, Tommaso

2013-04-16

Alveolar ridge keratosis (ARK) is a distinct, benign clinicopathological entity, characterized by a hyperkeratotic plaque or patch that occurs on the alveolar edentulous ridge or on the retromolar trigone, considered to be caused by chronic frictional trauma. The aim of this retrospective study is to present the clinicopathological features of 23 consecutive cases of ARK. The 23 biopsy samples of ARK were selected and pathological features were revised (keratosis, acanthosis, surface architecture, and inflammation). Factors such as the patient's gender, age, anatomical location, tobacco and alcohol use were analyzed. Sixteen out of the 23 cases studied were men and 7 women with a mean age of 55.05 (age ranged from 17 to 88 years). Thirteen cases had a history of tobacco habit, amongst whom, 4 also presented alcohol consumption. All the cases presented only unilateral lesions. Nineteen cases involved the retromolar trigone while 4 cases involved edentulous alveolar ridges. When observed microscopically, the lesions were mainly characterized by moderate to important hyperorthokeratosis. Inflammation was scanty or absent. In four of the cases, the presence of melanin pigment in the superficial corium or in the cytoplasm of macrophages was detected. None of the cases showed any features of dysplasia. Our results reveal that ARK is a benign lesion. However, the high prevalence of smokers amongst the patients might suggest that some potentially malignant disorders such as tobacco associated leukoplakia may clinically mimic ARK.

Resemblance of actin-binding protein/actin gels to covalently crosslinked networks

NASA Astrophysics Data System (ADS)

Janmey, Paul A.; Hvidt, Søren; Lamb, Jennifer; Stossel, Thomas P.

1990-05-01

THE maintainance of the shape of cells is often due to their surface elasticity, which arises mainly from an actin-rich cytoplasmic cortex1,2. On locomotion, phagocytosis or fission, however, these cells become partially fluid-like. The finding of proteins that can bind to actin and control the assembly of, or crosslink, actin filaments, and of intracellular messages that regulate the activities of some of these actin-binding proteins, indicates that such 'gel sol' transformations result from the rearrangement of cortical actin-rich networks3. Alternatively, on the basis of a study of the mechanical properties of mixtures of actin filaments and an Acanthamoeba actin-binding protein, α-actinin, it has been proposed that these transformations can be accounted for by rapid exchange of crosslinks between actin filaments4: the cortical network would be solid when the deformation rate is greater than the rate of crosslink exchange, but would deform or 'creep' when deformation is slow enough to permit crosslinker molecules to rearrange. Here we report, however, that mixtures of actin filaments and actin-binding protein (ABP), an actin crosslinking protein of many higher eukaryotes, form gels Theologically equivalent to covalently crosslinked networks. These gels do not creep in response to applied stress on a time scale compatible with most cell-surface movements. These findings support a more complex and controlled mechanism underlying the dynamic mechanical properties of cortical cytoplasm, and can explain why cells do not collapse under the constant shear forces that often exist in tissues.

A Case of Lymphomatoid Keratosis

PubMed Central

Choi, Min Jee; Kim, Hei Sung; Kim, Hyung Ok; Song, Kye Yong

2010-01-01

Lymphomatoid keratosis (LK) is considered to be a rare variant of cutaneous lymphoid hyperplasia, with epidermotropism. We herein report a case of LK which developed on the abdomen of an elderly Korean woman. A 60-year-old woman presented with a 10-year history of a pruritic, solitary, brown to black plaque on the abdomen. Histopathologically, the specimen showed hyperkeratosis, parakeratosis, acanthosis and Pautrier's micro-abscess in the epidermis, and a lichenoid infiltration of lymphocytes in the dermis, which expressed both B cell and T cell lineage on the immune-histochemical staining. Based on these clinical and histopathological findings, our case was diagnosed as LK. To our knowledge, this is the first case report of LK in the Korean dermatologic literature. PMID:20548920

Skin lesion removal

MedlinePlus

... benign; Cryosurgery - skin, benign; BCC - removal; Basal cell cancer - removal; Actinic keratosis - removal; Wart - removal; Squamous cell - removal; Mole - removal; Nevus - removal; Nevi - removal; Scissor ...

F-actin and G-actin binding are uncoupled by mutation of conserved tyrosine residues in maize actin depolymerizing factor (ZmADF)

PubMed Central

Jiang, Chang-Jie; Weeds, Alan G.; Khan, Safina; Hussey, Patrick J.

1997-01-01

Actin depolymerizing factors (ADF) are stimulus responsive actin cytoskeleton modulating proteins. They bind both monomeric actin (G-actin) and filamentous actin (F-actin) and, under certain conditions, F-actin binding is followed by filament severing. In this paper, using mutant maize ADF3 proteins, we demonstrate that the maize ADF3 binding of F-actin can be spatially distinguished from that of G-actin. One mutant, zmadf3–1, in which Tyr-103 and Ala-104 (equivalent to destrin Tyr-117 and Ala-118) have been replaced by phenylalanine and glycine, respectively, binds more weakly to both G-actin and F-actin compared with maize ADF3. A second mutant, zmadf3–2, in which both Tyr-67 and Tyr-70 are replaced by phenylalanine, shows an affinity for G-actin similar to maize ADF3, but F-actin binding is abolished. The two tyrosines, Tyr-67 and Tyr-70, are in the equivalent position to Tyr-82 and Tyr-85 of destrin, respectively. Using the tertiary structure of destrin, yeast cofilin, and Acanthamoeba actophorin, we discuss the implications of removing the aromatic hydroxyls of Tyr-82 and Tyr-85 (i.e., the effect of substituting phenylalanine for tyrosine) and conclude that Tyr-82 plays a critical role in stabilizing the tertiary structure that is essential for F-actin binding. We propose that this tertiary structure is maintained as a result of a hydrogen bond between the hydroxyl of Tyr-82 and the carbonyl of Tyr-117, which is located in the long α-helix; amino acid components of this helix (Leu-111 to Phe-128) have been implicated in G-actin and F-actin binding. The structures of human destrin and yeast cofilin indicate a hydrogen distance of 2.61 and 2.77 Å, respectively, with corresponding bond angles of 99.5° and 113°, close to the optimum for a strong hydrogen bond. PMID:9275236

Intracapsular tonsillectomy for keratosis pharyngeous: A pilot study of postoperative recovery and surgical efficacy.

PubMed

Gaudreau, Philip A; Gessler, Eric M

2017-09-01

Our objective was to perform a pilot study comparing intracapsular radiofrequency ablation tonsillectomy with subcapsular tonsillectomy in adult patients with keratosis pharyngeous. Patients diagnosed with keratosis pharyngeous between December 2010 and February 2013 were randomized to undergo either intracapsular or subcapsular tonsillectomy using radiofrequency ablation. Postoperative pain scores and amount of pain medication taken were recorded for 2 weeks. A 6-month follow-up questionnaire was used to assess efficacy of the procedure. Twenty-two patients completed the initial 2-week questionnaire. Eighteen completed the 6-month follow-up questionnaire. The amount of pain medication consumed on postoperative days 8 (p = 0.0293), 9 (p = 0.0146), and 10 (p = 0.035) was significantly less in the intracapsular group. Risk of recurrence of tonsilloliths was significantly greater at the 6-month follow-up in the intracapsular cohort (p = 0.0291). Based on these findings, in patients undergoing tonsillectomy for keratosis pharyngeous, intracapsular radiofrequency ablation tonsillectomy may result in decreased pain medication consumption compared with subcapsular tonsillectomy. Intracapsular tonsillectomy, however, resulted in a higher rate of recurrence of tonsilloliths. The benefit of decreased pain medication may be offset by the greater likelihood for symptoms to recur. Larger studies are needed to confirm these findings.

Actin turnover maintains actin filament homeostasis during cytokinetic ring contraction

PubMed Central

Palani, Saravanan; Sommese, Ruth; Kamnev, Anton; Hatano, Tomoyuki; Sivaramakrishnan, Sivaraj

2017-01-01

Cytokinesis in many eukaryotes involves a tension-generating actomyosin-based contractile ring. Many components of actomyosin rings turn over during contraction, although the significance of this turnover has remained enigmatic. Here, using Schizosaccharomyces japonicus, we investigate the role of turnover of actin and myosin II in its contraction. Actomyosin ring components self-organize into ∼1-µm-spaced clusters instead of undergoing full-ring contraction in the absence of continuous actin polymerization. This effect is reversed when actin filaments are stabilized. We tested the idea that the function of turnover is to ensure actin filament homeostasis in a synthetic system, in which we abolished turnover by fixing rings in cell ghosts with formaldehyde. We found that these rings contracted fully upon exogenous addition of a vertebrate myosin. We conclude that actin turnover is required to maintain actin filament homeostasis during ring contraction and that the requirement for turnover can be bypassed if homeostasis is achieved artificially. PMID:28655757

Synthetic peptides that cause F-actin bundling and block actin depolymerization

DOEpatents

Sederoff, Heike [Raleigh, NC; Huber, Steven C [Savoy, IL; Larabell, Carolyn A [Berkeley, CA

2011-10-18

Synthetic peptides derived from sucrose synthase, and having homology to actin and actin-related proteins, sharing a common motif, useful for causing acting bundling and preventing actin depolymerization. Peptides exhibiting the common motif are described, as well as specific synthetic peptides which caused bundled actin and inhibit actin depolymerization. These peptides can be useful for treating a subject suffering from a disease characterized by cells having neoplastic growth, for anti-cancer therapeutics, delivered to subjects solely, or concomitantly or sequentially with other known cancer therapeutics. These peptides can also be used for stabilizing microfilaments in living cells and inhibiting growth of cells.

76 FR 75447 - Amendment of Class E Airspace; Emmonak, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-02

.... * * * * * AAL AK E5 Emmonak, AK [Modified] Emmonak Airport, AK (Lat. 62[deg]47'10'' N., long. 164[deg]29'27'' W...-0880; Airspace Docket No. 11-AAL-17] Amendment of Class E Airspace; Emmonak, AK AGENCY: Federal... Emmonak, AK. The revision of two standard instrument approach procedures at the Emmonak Airport has made...

78 FR 16399 - Amendment of Class E Airspace; Unalakleet, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-15

..., AK (Lat. 63[deg]53'19'' N., long. 160[deg]47'57'' W.) That airspace within a 4.2-mile radius of.... * * * * * AAL AK E5 Unalakleet, AK [Modified] Unalakleet Airport, AK (Lat. 63[deg]53'19'' N., long. 160[deg]47...; Airspace Docket No. 12-AAL-3] Amendment of Class E Airspace; Unalakleet, AK AGENCY: Federal Aviation...

FGFR3, PIK3CA and RAS mutations in benign lichenoid keratosis.

PubMed

Groesser, L; Herschberger, E; Landthaler, M; Hafner, C

2012-04-01

Benign lichenoid keratoses (BLKs) are solitary skin lesions which have been proposed to represent a regressive form of pre-existent epidermal tumours such as solar lentigo or seborrhoeic keratosis. However, the genetic basis of BLK is unknown. FGFR3, PIK3CA and RAS mutations have been shown to be involved in the pathogenesis of seborrhoeic keratosis and solar lentigo. We thus investigated whether these mutations are also present in BLK. After manual microdissection and DNA isolation, 52 BLKs were screened for FGFR3, PIK3CA and RAS hotspot mutations using SNaPshot(®) multiplex assays. We identified 6/52 (12%) FGFR3 mutations, 10/52 (19%) PIK3CA mutations, 6/52 (12%) HRAS mutations and 2/52 (4%) KRAS mutations. FGFR3 and RAS mutations were mutually exclusive. One BLK showed a simultaneous PIK3CA and HRAS mutation. In nine BLKs with a mutation, nonlesional control tissue from the epidermal margin and the dermal lymphocytic infiltrate were wild-type, indicating that these mutations are somatic. To demonstrate that these findings are specific, 10 samples of lichen planus were analysed without evidence for FGFR3, PIK3CA or RAS mutations. Our results indicate that FGFR3, PIK3CA and RAS mutations are present in approximately 50% of BLKs. These findings support the concept on the molecular genetic level that at least a proportion of BLKs represents regressive variants resulting from former benign epidermal tumours such as seborrhoeic keratosis and solar lentigo. © 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.

75 FR 62459 - Revision of Class E Airspace; Unalakleet, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-12

...] Unalakleet Airport, AK (Lat. 63[deg]53'19'' N., long. 160[deg]47'57'' W.) Unalakleet Localizer (Lat. 63[deg]52'52'' N., long. 160[deg]47'42'' W.) Within a 4.2-mile radius of the Unalakleet Airport, AK, and.... * * * * * AAL AK E5 Unalakleet, AK [Revised] Unalakleet Airport, AK (Lat. 63[deg]53'19'' N., long. 160[deg]47'57...

Microscopy basics and the study of actin-actin-binding protein interactions.

PubMed

Thomasson, Maggie S; Macnaughtan, Megan A

2013-12-15

Actin is a multifunctional eukaryotic protein with a globular monomer form that polymerizes into a thin, linear microfilament in cells. Through interactions with various actin-binding proteins (ABPs), actin plays an active role in many cellular processes, such as cell motility and structure. Microscopy techniques are powerful tools for determining the role and mechanism of actin-ABP interactions in these processes. In this article, we describe the basic concepts of fluorescent speckle microscopy, total internal reflection fluorescence microscopy, atomic force microscopy, and cryoelectron microscopy and review recent studies that utilize these techniques to visualize the binding of actin with ABPs. Copyright © 2013 Elsevier Inc. All rights reserved.

Molecular architecture of the Spire-actin nucleus and its implication for actin filament assembly.

PubMed

Sitar, Tomasz; Gallinger, Julia; Ducka, Anna M; Ikonen, Teemu P; Wohlhoefler, Michael; Schmoller, Kurt M; Bausch, Andreas R; Joel, Peteranne; Trybus, Kathleen M; Noegel, Angelika A; Schleicher, Michael; Huber, Robert; Holak, Tad A

2011-12-06

The Spire protein is a multifunctional regulator of actin assembly. We studied the structures and properties of Spire-actin complexes by X-ray scattering, X-ray crystallography, total internal reflection fluorescence microscopy, and actin polymerization assays. We show that Spire-actin complexes in solution assume a unique, longitudinal-like shape, in which Wiskott-Aldrich syndrome protein homology 2 domains (WH2), in an extended configuration, line up actins along the long axis of the core of the Spire-actin particle. In the complex, the kinase noncatalytic C-lobe domain is positioned at the side of the first N-terminal Spire-actin module. In addition, we find that preformed, isolated Spire-actin complexes are very efficient nucleators of polymerization and afterward dissociate from the growing filament. However, under certain conditions, all Spire constructs--even a single WH2 repeat--sequester actin and disrupt existing filaments. This molecular and structural mechanism of actin polymerization by Spire should apply to other actin-binding proteins that contain WH2 domains in tandem.

Molecular architecture of the Spire–actin nucleus and its implication for actin filament assembly

PubMed Central

Sitar, Tomasz; Gallinger, Julia; Ducka, Anna M.; Ikonen, Teemu P.; Wohlhoefler, Michael; Schmoller, Kurt M.; Bausch, Andreas R.; Joel, Peteranne; Trybus, Kathleen M.; Noegel, Angelika A.; Schleicher, Michael; Huber, Robert; Holak, Tad A.

2011-01-01

The Spire protein is a multifunctional regulator of actin assembly. We studied the structures and properties of Spire–actin complexes by X-ray scattering, X-ray crystallography, total internal reflection fluorescence microscopy, and actin polymerization assays. We show that Spire–actin complexes in solution assume a unique, longitudinal-like shape, in which Wiskott–Aldrich syndrome protein homology 2 domains (WH2), in an extended configuration, line up actins along the long axis of the core of the Spire–actin particle. In the complex, the kinase noncatalytic C-lobe domain is positioned at the side of the first N-terminal Spire–actin module. In addition, we find that preformed, isolated Spire–actin complexes are very efficient nucleators of polymerization and afterward dissociate from the growing filament. However, under certain conditions, all Spire constructs—even a single WH2 repeat—sequester actin and disrupt existing filaments. This molecular and structural mechanism of actin polymerization by Spire should apply to other actin-binding proteins that contain WH2 domains in tandem. PMID:22106272

Potential Role of S100A8 in Cutaneous Squamous Cell Carcinoma Differentiation

PubMed Central

Shin, Jung-Min; Chang, In-Kyu; Lee, Young-Ho; Yeo, Min-Kyung; Kim, Jin-Man; Sohn, Kyung-Cheol; Im, Myung; Seo, Young-Joon; Kim, Chang-Deok; Lee, Jeung-Hoon

2016-01-01

Background S100A8 is differentially expressed in various cell types and is associated with a number of malignant disorders. S100A8 may affect tumor biology. However, its role in cutaneous squamous cell carcinoma (SCC) is not well established. Objective This study aims to investigate the relationship between S100A8 and cutaneous SCC development. Methods We performed immunohistochemical staining to detect S100A8 expression in facial skin specimens of premalignant actinic keratosis (AK), malignant SCC, and normal tissues. In addition, we utilized postconfluence and high calcium-induced differentiation in a culture system model. Furthermore, we constructed a recombinant adenovirus expressing GFP-tagged S100A8 to investigate the role of S100A8 in SCC cell differentiation. Results S100A8 was significantly overexpressed in human cutaneous SCC compared to that in normal and AK tissues. S100A8 was gradually upregulated in SCC cells in a post-confluence-induced differentiation model. Overexpression of S100A8 in SCC cells induced by adenoviral transduction led to increased expression levels of differentiation markers, such as loricrin, involucrin, and filaggrin. S100A8 overexpression also increased loricrin and involucrin luciferase activity. Conclusion S100A8 regulates cutaneous SCC differentiation and induces well-differentiated SCC formation in skin. PMID:27081264

Glycophenotype Evaluation in Cutaneous Tumors Using Lectins Labeled with Acridinium Ester

PubMed Central

Lima, Luiza Rayanna Amorim; Almeida, Sinara Mônica Vitalino; Silva, Lúcia Patrícia Bezerra Gomes; Beltrão, Eduardo Isidoro Carneiro; Carvalho Júnior, Luiz Bezerra

2013-01-01

Background. Tumor cells show alterations in their glycosylation patterns when compared to normal cells. Lectins can be used to evaluate these glycocode changes. Chemiluminescence assay is an effective technique for quantitative analysis of proteins, nucleic acids, and carbohydrates due to its high sensitivity, specificity, and rapid testing. Objective. To use histochemiluminescence based on lectin conjugated to acridinium ester (AE) for the investigation of glycophenotype changes in cutaneous tumors. Methods. Concanavalin A (Con A), Peanut agglutinin (PNA), Ulex europaeus agglutinin-I (UEA-I), and Maackia amurensis agglutinin (MAA) were conjugated to acridinium ester. Biopsies of cutaneous tumors and normal skin were incubated with the lectins-AE, and chemiluminescence was quantified and expressed as Relative Light Units (RLU). Results. Actinic keratosis (AK), keratoacanthoma (KA), squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) showed lower expression of α-D-glucose/mannose and α-L-fucose residues compared to normal tissue. Cutaneous tumors displayed higher expression of Gal-β(1-3)-GalNAc residues than normal tissue. AK and SCC exhibited higher expression of Neu5Ac-α(2,3)Gal residues than normal epidermis. KA and BCC showed equivalent RLU values compared to normal tissue. Conclusions. Lectin histochemiluminescence allowed quantitative assessment of the carbohydrate expression in cutaneous tissues, contributing to eliminate the subjectivity of conventional techniques used in the histopathological diagnosis. PMID:24167360

Clinical study of a retinoic acid-loaded microneedle patch for seborrheic keratosis or senile lentigo.

PubMed

Hirobe, Sachiko; Otsuka, Risa; Iioka, Hiroshi; Quan, Ying-Shu; Kamiyama, Fumio; Asada, Hideo; Okada, Naoki; Nakagawa, Shinsaku

2017-01-01

Pigmented lesions such as of seborrheic keratosis and senile lentigo, which are commonly seen on skin of people>50years of age, are considered unattractive and disfiguring because of their negative psychological impact. Drug therapy using all-trans retinoic acid (ATRA) is an attractive option for self-treatment at home. We have developed an ATRA-loaded microneedle patch (ATRA-MN) and confirmed the pharmacological effects of ATRA-MN application in mice. Here, we describe a clinical study to evaluate the safety and efficacy of ATRA-MN in subjects with seborrheic keratosis or senile lentigo. ATRA-MN was applied to the lesion site of each subject for 6h once per week for 4weeks. The skin irritation reaction was scored to assess adverse reactions and blood tests were performed to evaluate the presence of systemic adverse reactions. To assess the treatment effect using ATRA-MN, the desquamation and whitening ability of the investigational skin was observed. Desquamation of the stratum corneum was observed following four ATRA-MN applications at 1-week intervals, but ATRA-MN applications did not induce severe local or systemic adverse effects. These results showed that ATRA-MN treatment is promising as a safe and effective therapy for seborrheic keratosis and senile lentigo. Copyright © 2016 Elsevier Inc. All rights reserved.

Cofilin Changes the Twist of F-Actin: Implications for Actin Filament Dynamics and Cellular Function

PubMed Central

McGough, Amy; Pope, Brian; Chiu, Wah; Weeds, Alan

1997-01-01

Cofilin is an actin depolymerizing protein found widely distributed in animals and plants. We have used electron cryomicroscopy and helical reconstruction to identify its binding site on actin filaments. Cofilin binds filamentous (F)-actin cooperatively by bridging two longitudinally associated actin subunits. The binding site is centered axially at subdomain 2 of the lower actin subunit and radially at the cleft between subdomains 1 and 3 of the upper actin subunit. Our work has revealed a totally unexpected (and unique) property of cofilin, namely, its ability to change filament twist. As a consequence of this change in twist, filaments decorated with cofilin have much shorter ‘actin crossovers' (∼75% of those normally observed in F-actin structures). Although their binding sites are distinct, cofilin and phalloidin do not bind simultaneously to F-actin. This is the first demonstration of a protein that excludes another actin-binding molecule by changing filament twist. Alteration of F-actin structure by cofilin/ADF appears to be a novel mechanism through which the actin cytoskeleton may be regulated or remodeled. PMID:9265645

Actin-interacting Protein 1 Promotes Disassembly of Actin-depolymerizing Factor/Cofilin-bound Actin Filaments in a pH-dependent Manner.

PubMed

Nomura, Kazumi; Hayakawa, Kimihide; Tatsumi, Hitoshi; Ono, Shoichiro

2016-03-04

Actin-interacting protein 1 (AIP1) is a conserved WD repeat protein that promotes disassembly of actin filaments when actin-depolymerizing factor (ADF)/cofilin is present. Although AIP1 is known to be essential for a number of cellular events involving dynamic rearrangement of the actin cytoskeleton, the regulatory mechanism of the function of AIP1 is unknown. In this study, we report that two AIP1 isoforms from the nematode Caenorhabditis elegans, known as UNC-78 and AIPL-1, are pH-sensitive in enhancement of actin filament disassembly. Both AIP1 isoforms only weakly enhance disassembly of ADF/cofilin-bound actin filaments at an acidic pH but show stronger disassembly activity at neutral and basic pH values. However, a severing-defective mutant of UNC-78 shows pH-insensitive binding to ADF/cofilin-decorated actin filaments, suggesting that the process of filament severing or disassembly, but not filament binding, is pH-dependent. His-60 of AIP1 is located near the predicted binding surface for the ADF/cofilin-actin complex, and an H60K mutation of AIP1 partially impairs its pH sensitivity, suggesting that His-60 is involved in the pH sensor for AIP1. These biochemical results suggest that pH-dependent changes in AIP1 activity might be a novel regulatory mechanism of actin filament dynamics. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Torsional Rigidity of Single Actin Filaments and Actin-Actin Bond Breaking Force under Torsion Measured Directly by in vitro Micromanipulation

NASA Astrophysics Data System (ADS)

Tsuda, Yuri; Yasutake, Hironori; Ishijima, Akihiko; Yanagida, Toshio

1996-11-01

Knowledge of the elastic properties of actin filaments is crucial for considering its role in muscle contraction, cellular motile events, and formation of cell shape. The stiffness of actin filaments in the directions of stretching and bending has been determined. In this study, we have directly determined the torsional rigidity and breaking force of single actin filaments by measuring the rotational Brownian motion and tensile strength using optical tweezers and microneedles, respectively. Rotational angular fluctuations of filaments supplied the torsional rigidity as (8.0 ± 1.2) × 10-26 Nm2. This value is similar to that deduced from the longitudinal rigidity, assuming the actin filament to be a homogeneous rod. The breaking force of the actin-actin bond was measured while twisting a filament through various angles using microneedles. The breaking force decreased greatly under twist, e.g., from 600-320 pN when filaments were turned through 90 degrees, independent of the rotational direction. Our results indicate that an actin filament exhibits comparable flexibility in the rotational and longitudinal directions, but breaks more easily under torsional load.

[Keratosis palmoplantaris maculosa seu papulosa (Davies-Colley) simulating multiple cornua cutanea].

PubMed

Schreiber, D; Stücker, M; Hoffmann, K; Bacharach-Buhles, M; Altmeyer, P

1997-08-01

Patient with extensive keratosis palmoplantaris maculosa seu papulosa (Davies-Colley) presented with multiple cutaneous horns. The clinical picture, the histology, the electro microscopic examination, the negative tumor screening and the viral classification in the tissue allowed the differentiation from other palmoplantar keratoses. The patient was treated successfully using a combination of acitretin with physical and chemical measures.

76 FR 54148 - Proposed Amendment of Class E Airspace; Emmonak, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-31

... AK E5 Emmonak, AK [Revised] Emmonak Airport, AK (Lat. 62[deg]47'10'' N., long. 164[deg]29'27'' W...-0880 Airspace Docket No. 11-AAL-17] Proposed Amendment of Class E Airspace; Emmonak, AK AGENCY: Federal... proposes to revise Class E airspace at Emmonak, AK. The amendment of two standard instrument approach...

Myopodin is an F-actin bundling protein with multiple independent actin-binding regions.

PubMed

Linnemann, Anja; Vakeel, Padmanabhan; Bezerra, Eduardo; Orfanos, Zacharias; Djinović-Carugo, Kristina; van der Ven, Peter F M; Kirfel, Gregor; Fürst, Dieter O

2013-02-01

The assembly of striated muscle myofibrils is a multistep process in which a variety of proteins is involved. One of the first and most important steps in myofibrillogenesis is the arrangement of thin myofilaments into ordered I-Z-I brushes, requiring the coordinated activity of numerous actin binding proteins. The early expression of myopodin prior to sarcomeric α-actinin, as well as its binding to actin, α-actinin and filamin indicate an important role for this protein in actin cytoskeleton remodelling with the precise function of myopodin in this process yet remaining to be resolved. While myopodin was previously described as a protein capable of cross-linking actin filaments into thick bundles upon transient transfections, it has remained unclear whether myopodin alone is capable of bundling actin, or if additional proteins are involved. We have therefore investigated the in vitro actin binding properties of myopodin. High speed cosedimentation assays with skeletal muscle actin confirmed direct binding of myopodin to F-actin and showed that this interaction is mediated by at least two independent actin binding sites, found in all myopodin isoforms identified to date. Furthermore, low-speed cosedimentation assays revealed that not only full length myopodin, but also the fragment containing only the second binding site, bundles microfilaments in the absence of accessory proteins. Ultrastructural analysis demonstrated that this bundling activity resembled that of α-actinin. Biochemical experiments revealed that bundling was not achieved by myopodin's ability to dimerize, indicating the presence of two individual F-actin binding sites within the second binding segment. Thus full length myopodin contains at least three F-actin binding sites. These data provide further understanding of the mechanisms by which myopodin contributes to actin reorganization during myofibril assembly.

Differentiation of seborrheic keratosis from basal cell carcinoma, nevi and melanoma by RGB autofluorescence imaging

PubMed Central

Lihachev, Alexey; Lihacova, Ilze; Plorina, Emilija V.; Lange, Marta; Derjabo, Alexander; Spigulis, Janis

2018-01-01

A clinical trial on the autofluorescence imaging of skin lesions comprising 16 dermatologically confirmed pigmented nevi, 15 seborrheic keratosis, 2 dysplastic nevi, histologically confirmed 17 basal cell carcinomas and 1 melanoma was performed. The autofluorescence spatial properties of the skin lesions were acquired by smartphone RGB camera under 405 nm LED excitation. The diagnostic criterion is based on the calculation of the mean autofluorescence intensity of the examined lesion in the spectral range of 515 nm–700 nm. The proposed methodology is able to differentiate seborrheic keratosis from basal cell carcinoma, pigmented nevi and melanoma. The sensitivity and specificity of the proposed method was estimated as being close to 100%. The proposed methodology and potential clinical applications are discussed in this article. PMID:29675324

Differentiation of seborrheic keratosis from basal cell carcinoma, nevi and melanoma by RGB autofluorescence imaging.

PubMed

Lihachev, Alexey; Lihacova, Ilze; Plorina, Emilija V; Lange, Marta; Derjabo, Alexander; Spigulis, Janis

2018-04-01

A clinical trial on the autofluorescence imaging of skin lesions comprising 16 dermatologically confirmed pigmented nevi, 15 seborrheic keratosis, 2 dysplastic nevi, histologically confirmed 17 basal cell carcinomas and 1 melanoma was performed. The autofluorescence spatial properties of the skin lesions were acquired by smartphone RGB camera under 405 nm LED excitation. The diagnostic criterion is based on the calculation of the mean autofluorescence intensity of the examined lesion in the spectral range of 515 nm-700 nm. The proposed methodology is able to differentiate seborrheic keratosis from basal cell carcinoma, pigmented nevi and melanoma. The sensitivity and specificity of the proposed method was estimated as being close to 100%. The proposed methodology and potential clinical applications are discussed in this article.

Nucleation of actin polymerization by gelsolin.

PubMed

Ditsch, A; Wegner, A

1994-08-15

The time-course of assembly of actin with gelsolin was measured by the fluorescence increase of a fluorescent label covalently linked to actin. The actin concentrations ranged from values far below the critical concentration to values above the critical concentration of the pointed ends of actin filaments. If the concentration of actin was in the range of the critical monomer concentration (0.64 microM), the time-course of the concentration of actin assembled with gelsolin revealed a sigmoidal shape. At higher actin concentrations the time-course of association of actin with gelsolin approximated an exponential curve. The measured time-courses of assembly were quantitatively interpreted by kinetic rate equations. A poor fit was obtained if two actin molecules were assumed to bind to gelsolin to form a 1:2 gelsolin-actin complex and subsequently further actin molecules were assumed to polymerize onto the 1:2 gelsolin-actin complex toward the pointed end. A considerably better agreement between calculated and measured time-courses was achieved if additional creation of actin filaments by fast fragmentation of newly formed actin filaments by not yet consumed gelsolin was assumed to occur. This suggests that both polymerization of actin onto gelsolin and fragmentation of actin filaments contribute to formation of new actin filaments by gelsolin. Furthermore it could be demonstrated that below the critical monomer concentration appreciable amounts of actin are incorporated into gelsolin-actin oligomers.

75 FR 32865 - Proposed Revision of Class E Airspace; Unalakleet, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-10

...] Unalakleet Airport, AK (Lat. 63[deg]53'19'' N., long. 160[deg]47'57'' W.) Unalakleet Localizer (Lat. 63[deg]52'52'' N., long. 160[deg]47'42'' W.) Within a 4.2-mile radius of the Unalakleet Airport, AK, and.... * * * * * AAL AK E5 Unalakleet, AK [Revised] Unalakleet Airport, AK (Lat. 63[deg]53'19'' N., long. 160[deg]47'57...

75 FR 44884 - Revision of Class E Airspace; Kulik Lake, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-30

... Regulations (14 CFR) part 71 by revising Class E airspace at Kulik Lake Airport, AK, to correct an old... More Above the Surface of the Earth * * * * * AAL AK E5 Kulik Lake, AK [Revised] Kulik Lake Airport, AK...

PI(3,5)P2 controls endosomal branched actin dynamics by regulating cortactin–actin interactions

PubMed Central

Hong, Nan Hyung; Qi, Aidong

2015-01-01

Branched actin critically contributes to membrane trafficking by regulating membrane curvature, dynamics, fission, and transport. However, how actin dynamics are controlled at membranes is poorly understood. Here, we identify the branched actin regulator cortactin as a direct binding partner of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) and demonstrate that their interaction promotes turnover of late endosomal actin. In vitro biochemical studies indicated that cortactin binds PI(3,5)P2 via its actin filament-binding region. Furthermore, PI(3,5)P2 competed with actin filaments for binding to cortactin, thereby antagonizing cortactin activity. These findings suggest that PI(3,5)P2 formation on endosomes may remove cortactin from endosome-associated branched actin. Indeed, inhibition of PI(3,5)P2 production led to cortactin accumulation and actin stabilization on Rab7+ endosomes. Conversely, inhibition of Arp2/3 complex activity greatly reduced cortactin localization to late endosomes. Knockdown of cortactin reversed PI(3,5)P2-inhibitor–induced actin accumulation and stabilization on endosomes. These data suggest a model in which PI(3,5)P2 binding removes cortactin from late endosomal branched actin networks and thereby promotes net actin turnover. PMID:26323691

Actin stress in cell reprogramming

PubMed Central

Guo, Jun; Wang, Yuexiu; Sachs, Frederick; Meng, Fanjie

2014-01-01

Cell mechanics plays a role in stem cell reprogramming and differentiation. To understand this process better, we created a genetically encoded optical probe, named actin–cpstFRET–actin (AcpA), to report forces in actin in living cells in real time. We showed that stemness was associated with increased force in actin. We reprogrammed HEK-293 cells into stem-like cells using no transcription factors but simply by softening the substrate. However, Madin-Darby canine kidney (MDCK) cell reprogramming required, in addition to a soft substrate, Harvey rat sarcoma viral oncogene homolog expression. Replating the stem-like cells on glass led to redifferentiation and reduced force in actin. The actin force probe was a FRET sensor, called cpstFRET (circularly permuted stretch sensitive FRET), flanked by g-actin subunits. The labeled actin expressed efficiently in HEK, MDCK, 3T3, and bovine aortic endothelial cells and in multiple stable cell lines created from those cells. The viability of the cell lines demonstrated that labeled actin did not significantly affect cell physiology. The labeled actin distribution was similar to that observed with GFP-tagged actin. We also examined the stress in the actin cross-linker actinin. Actinin force was not always correlated with actin force, emphasizing the need for addressing protein specificity when discussing forces. Because actin is a primary structural protein in animal cells, understanding its force distribution is central to understanding animal cell physiology and the many linked reactions such as stress-induced gene expression. This new probe permits measuring actin forces in a wide range of experiments on preparations ranging from isolated proteins to transgenic animals. PMID:25422450

Treatment of Actinic Purpura

PubMed Central

2017-01-01

Mature skin is prone to bruising, resulting in a condition known as actinic purpura, characterized by unsightly ecchymosis and purple patches. Similar to other skin conditions, the incidence of actinic purpura increases with advancing age and occurs with equal frequency among men and women. The unsightly appearance of actinic purpura may be a source of emotional distress among the elderly. A new product has been formulated specifically for the treatment of actinic purpura. This product contains retinol, α-hydroxy acids, arnica oil, ceramides, niacinamide, and phytonadione, which effectively treat actinic purpura by improving local circulation, thickening the skin, and repairing the skin barrier. The objective of this paper is to review the beneficial properties of these ingredients and their respective roles in the treatment of actinic purpura. PMID:28979656

Actin assembly factors regulate the gelation kinetics and architecture of F-actin networks.

PubMed

Falzone, Tobias T; Oakes, Patrick W; Sees, Jennifer; Kovar, David R; Gardel, Margaret L

2013-04-16

Dynamic regulation of the actin cytoskeleton is required for diverse cellular processes. Proteins regulating the assembly kinetics of the cytoskeletal biopolymer F-actin are known to impact the architecture of actin cytoskeletal networks in vivo, but the underlying mechanisms are not well understood. Here, we demonstrate that changes to actin assembly kinetics with physiologically relevant proteins profilin and formin (mDia1 and Cdc12) have dramatic consequences on the architecture and gelation kinetics of otherwise biochemically identical cross-linked F-actin networks. Reduced F-actin nucleation rates promote the formation of a sparse network of thick bundles, whereas increased nucleation rates result in a denser network of thinner bundles. Changes to F-actin elongation rates also have marked consequences. At low elongation rates, gelation ceases and a solution of rigid bundles is formed. By contrast, rapid filament elongation accelerates dynamic arrest and promotes gelation with minimal F-actin density. These results are consistent with a recently developed model of how kinetic constraints regulate network architecture and underscore how molecular control of polymer assembly is exploited to modulate cytoskeletal architecture and material properties. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

The pros and cons of common actin labeling tools for visualizing actin dynamics during Drosophila oogenesis

PubMed Central

Spracklen, Andrew J.; Fagan, Tiffany N.; Lovander, Kaylee E.; Tootle, Tina L.

2015-01-01

Dynamic remodeling of the actin cytoskeleton is required for both development and tissue homeostasis. While fixed image analysis has provided significant insight into such events, a complete understanding of cytoskeletal dynamics requires live imaging. Numerous tools for the live imaging of actin have been generated by fusing the actin-binding domain from an actin-interacting protein to a fluorescent protein. Here we comparatively assess the utility of three such tools – Utrophin, Lifeact, and F-tractin – for characterizing the actin remodeling events occurring within the germline-derived nurse cells during Drosophila mid-oogenesis or follicle development. Specifically, we used the UAS/GAL4 system to express these tools at different levels and in different cells, and analyzed these tools for effects on fertility, alterations in the actin cytoskeleton, and ability to label filamentous actin (F-actin) structures by both fixed and live imaging. While both Utrophin and Lifeact robustly label F-actin structures within the Drosophila germline, when strongly expressed they cause sterility and severe actin defects including cortical actin breakdown resulting in multi-nucleate nurse cells, early F-actin filament and aggregate formation during stage 9 (S9), and disorganized parallel actin filament bundles during stage 10B (S10B). However, by using a weaker germline GAL4 driver in combination with a higher temperature, Utrophin can label F-actin with minimal defects. Additionally, strong Utrophin expression within the germline causes F-actin formation in the nurse cell nuclei and germinal vesicle during mid-oogenesis. Similarly, Lifeact expression results in nuclear F-actin only within the germinal vesicle. F-tractin expresses at a lower level than the other two labeling tools, but labels cytoplasmic F-actin structures well without causing sterility or striking actin defects. Together these studies reveal how critical it is to evaluate the utility of each actin labeling

Adenylate kinase 2 (AK2) promotes cell proliferation in insect development

PubMed Central

2012-01-01

Background Adenylate kinase 2 (AK2) is a phosphotransferase that catalyzes the reversible reaction 2ADP(GDP) ↔ ATP(GTP) + AMP and influences cellular energy homeostasis. However, the role of AK2 in regulating cell proliferation remains unclear because AK2 has been reported to be involved in either cell proliferation or cell apoptosis in different cell types of various organisms. Results This study reports AK2 promotion of cell proliferation using the lepidopteran insect Helicoverpa armigera and its epidermal cell line HaEpi as models. Western blot analysis indicates that AK2 constitutively expresses in various tissues during larval development. Immunocytochemistry analysis indicates that AK2 localizes in the mitochondria. The recombinant expressed AK2 in E. coli promotes cell growth and viability of HaEpi cell line by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. AK2 knockdown in larvae by RNA interference causes larval growth defects, including body weight decrease and development delay. AK2 knockdown in larvae also decreases the number of circulating haemocytes. The mechanism for such effects might be the suppression of gene transcription involved in insect development caused by AK2 knockdown. Conclusion These results show that AK2 regulates cell growth, viability, and proliferation in insect growth and development. PMID:23020757

The yeast actin cytoskeleton.

PubMed

Mishra, Mithilesh; Huang, Junqi; Balasubramanian, Mohan K

2014-03-01

The actin cytoskeleton is a complex network of dynamic polymers, which plays an important role in various fundamental cellular processes, including maintenance of cell shape, polarity, cell division, cell migration, endocytosis, vesicular trafficking, and mechanosensation. Precise spatiotemporal assembly and disassembly of actin structures is regulated by the coordinated activity of about 100 highly conserved accessory proteins, which nucleate, elongate, cross-link, and sever actin filaments. Both in vivo studies in a wide range of organisms from yeast to metazoans and in vitro studies of purified proteins have helped shape the current understanding of actin dynamics and function. Molecular genetics, genome-wide functional analysis, sophisticated real-time imaging, and ultrastructural studies in concert with biochemical analysis have made yeast an attractive model to understand the actin cytoskeleton, its molecular dynamics, and physiological function. Studies of the yeast actin cytoskeleton have contributed substantially in defining the universal mechanism regulating actin assembly and disassembly in eukaryotes. Here, we review some of the important insights generated by the study of actin cytoskeleton in two important yeast models the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

75 FR 32652 - Revocation and Establishment of Class E Airspace; Nuiqsut, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-09

...-0502; Airspace Docket No. 10-AAL-15] Revocation and Establishment of Class E Airspace; Nuiqsut, AK... establishes Class E airspace on the north slope of Alaska near Nuiqsut, AK, to provide controlled airspace to..., Pioneer Heliport (AA27), Nuiqsut, AK, and Oooguruk Island Heliport (AK32), Nuiqsut, AK, both formerly...

Co-transcriptional nuclear actin dynamics

PubMed Central

Percipalle, Piergiorgio

2013-01-01

Actin is a key player for nuclear structure and function regulating both chromosome organization and gene activity. In the cell nucleus actin interacts with many different proteins. Among these proteins several studies have identified classical nuclear factors involved in chromatin structure and function, transcription and RNA processing as well as proteins that are normally involved in controlling the actin cytoskeleton. These discoveries have raised the possibility that nuclear actin performs its multi task activities through tight interactions with different sets of proteins. This high degree of promiscuity in the spectrum of protein-to-protein interactions correlates well with the conformational plasticity of actin and the ability to undergo regulated changes in its polymerization states. Several of the factors involved in controlling head-to-tail actin polymerization have been shown to be in the nucleus where they seem to regulate gene activity. By focusing on the multiple tasks performed by actin and actin-binding proteins, possible models of how actin dynamics controls the different phases of the RNA polymerase II transcription cycle are being identified. PMID:23138849

Adhesive F-actin Waves: A Novel Integrin-Mediated Adhesion Complex Coupled to Ventral Actin Polymerization

PubMed Central

Case, Lindsay B.; Waterman, Clare M.

2011-01-01

At the leading lamellipodium of migrating cells, protrusion of an Arp2/3-nucleated actin network is coupled to formation of integrin-based adhesions, suggesting that Arp2/3-mediated actin polymerization and integrin-dependent adhesion may be mechanistically linked. Arp2/3 also mediates actin polymerization in structures distinct from the lamellipodium, in “ventral F-actin waves” that propagate as spots and wavefronts along the ventral plasma membrane. Here we show that integrins engage the extracellular matrix downstream of ventral F-actin waves in several mammalian cell lines as well as in primary mouse embryonic fibroblasts. These “adhesive F-actin waves” require a cycle of integrin engagement and disengagement to the extracellular matrix for their formation and propagation, and exhibit morphometry and a hierarchical assembly and disassembly mechanism distinct from other integrin-containing structures. After Arp2/3-mediated actin polymerization, zyxin and VASP are co-recruited to adhesive F-actin waves, followed by paxillin and vinculin, and finally talin and integrin. Adhesive F-actin waves thus represent a previously uncharacterized integrin-based adhesion complex associated with Arp2/3-mediated actin polymerization. PMID:22069459

Filopodia-like Actin Cables Position Nuclei in Association with Perinuclear Actin in Drosophila Nurse Cells

PubMed Central

Huelsmann, Sven; Ylänne, Jari; Brown, Nicholas H.

2013-01-01

Summary Controlling the position of the nucleus is vital for a number of cellular processes from yeast to humans. In Drosophila nurse cells, nuclear positioning is crucial during dumping, when nurse cells contract and expel their contents into the oocyte. We provide evidence that in nurse cells, continuous filopodia-like actin cables, growing from the plasma membrane and extending to the nucleus, achieve nuclear positioning. These actin cables move nuclei away from ring canals. When nurse cells contract, actin cables associate laterally with the nuclei, in some cases inducing nuclear turning so that actin cables become partially wound around the nuclei. Our data suggest that a perinuclear actin meshwork connects actin cables to nuclei via actin-crosslinking proteins such as the filamin Cheerio. We provide a revised model for how actin structures position nuclei in nurse cells, employing evolutionary conserved machinery. PMID:24091012

Nucleus-associated actin in Amoeba proteus.

PubMed

Berdieva, Mariia; Bogolyubov, Dmitry; Podlipaeva, Yuliya; Goodkov, Andrew

2016-10-01

The presence, spatial distribution and forms of intranuclear and nucleus-associated cytoplasmic actin were studied in Amoeba proteus with immunocytochemical approaches. Labeling with different anti-actin antibodies and staining with TRITC-phalloidin and fluorescent deoxyribonuclease I were used. We showed that actin is abundant within the nucleus as well as in the cytoplasm of A. proteus cells. According to DNase I experiments, the predominant form of intranuclear actin is G-actin which is associated with chromatin strands. Besides, unpolymerized actin was shown to participate in organization of a prominent actin layer adjacent to the outer surface of nuclear envelope. No significant amount of F-actin was found in the nucleus. At the same time, the amoeba nucleus is enclosed in a basket-like structure formed by circumnuclear actin filaments and bundles connected with global cytoplasmic actin cytoskeleton. A supposed architectural function of actin filaments was studied by treatment with actin-depolymerizing agent latrunculin A. It disassembled the circumnuclear actin system, but did not affect the intranuclear chromatin structure. The results obtained for amoeba cells support the modern concept that actin is involved in fundamental nuclear processes that have evolved in the cells of multicellular organisms. Copyright © 2016 Elsevier GmbH. All rights reserved.

Papular, profuse, and precocious keratosis pilaris.

PubMed

Castela, Emeline; Chiaverini, Christine; Boralevi, Franck; Hugues, Rosalind; Lacour, Jean Philippe

2012-01-01

Keratosis pilaris (KP) is a frequent and benign condition in children characterized by the presence of rough, follicular papules and varying degrees of erythema. Different variants have been described, including simple KP and red KP. Between September 2007 and October 2010, 11 children with profuse and precocious KP seen at the department of pediatric dermatology were included. They defined an underemphasized clinical variant of childhood KP: the papular, profuse, and precocious KP characterized by early age of onset (<18 mos), extensive involvement of the limbs and cheeks, and papular nature of lesions. No clinical association has been found. The main complication was episodes of folliculitis. Diagnosis was delayed for all patients. Treatment is difficult, but association between emollient and keratolytic agents can provide some help. © 2011 Wiley Periodicals, Inc.

Actin Assembly Factors Regulate the Gelation Kinetics and Architecture of F-actin Networks

PubMed Central

Falzone, Tobias T.; Oakes, Patrick W.; Sees, Jennifer; Kovar, David R.; Gardel, Margaret L.

2013-01-01

Dynamic regulation of the actin cytoskeleton is required for diverse cellular processes. Proteins regulating the assembly kinetics of the cytoskeletal biopolymer F-actin are known to impact the architecture of actin cytoskeletal networks in vivo, but the underlying mechanisms are not well understood. Here, we demonstrate that changes to actin assembly kinetics with physiologically relevant proteins profilin and formin (mDia1 and Cdc12) have dramatic consequences on the architecture and gelation kinetics of otherwise biochemically identical cross-linked F-actin networks. Reduced F-actin nucleation rates promote the formation of a sparse network of thick bundles, whereas increased nucleation rates result in a denser network of thinner bundles. Changes to F-actin elongation rates also have marked consequences. At low elongation rates, gelation ceases and a solution of rigid bundles is formed. By contrast, rapid filament elongation accelerates dynamic arrest and promotes gelation with minimal F-actin density. These results are consistent with a recently developed model of how kinetic constraints regulate network architecture and underscore how molecular control of polymer assembly is exploited to modulate cytoskeletal architecture and material properties. PMID:23601318

United States Food and Drug Administration Product Label Changes.

PubMed

Kircik, Leon; Sung, Julie C; Stein-Gold, Linda; Goldenberg, Gary

2017-02-01

Once a drug has been approved by the United States Food and Drug Administration and is on the market, the Food and Drug Administration communicates new safety information through product label changes. Most of these label changes occur after a spontaneous report to either the drug manufacturing companies or the Food and Drug Administration MedWatch program. As a result, 400 to 500 label changes occur every year. Actinic keratosis treatments exemplify the commonality of label changes throughout the postmarket course of a drug. Diclofenac gel, 5-fluorouracil cream, imiquimod, and ingenol mebutate are examples of actinic keratosis treatments that have all undergone at least one label revision. With the current system of spontaneous reports leading to numerous label changes, each occurrence does not necessarily signify a radical change in the safety of a drug.

A new F-actin structure in fungi: actin ring formation around the cell nucleus of Cryptococcus neoformans.

PubMed

Kopecká, Marie; Kawamoto, Susumu; Yamaguchi, Masashi

2013-04-01

The F-actin cytoskeleton of Cryptococcus neoformans is known to comprise actin cables, cortical patches and cytokinetic ring. Here, we describe a new F-actin structure in fungi, a perinuclear F-actin collar ring around the cell nucleus, by fluorescent microscopic imaging of rhodamine phalloidin-stained F-actin. Perinuclear F-actin rings form in Cryptococcus neoformans treated with the microtubule inhibitor Nocodazole or with the drug solvent dimethyl sulfoxide (DMSO) or grown in yeast extract peptone dextrose (YEPD) medium, but they are absent in cells treated with Latrunculin A. Perinuclear F-actin rings may function as 'funicular cabin' for the cell nucleus, and actin cables as intracellular 'funicular' suspending nucleus in the central position in the cell and moving nucleus along the polarity axis along actin cables.

Interventions for actinic keratoses.

PubMed

Gupta, Aditya K; Paquet, Maryse; Villanueva, Elmer; Brintnell, William

2012-12-12

Actinic keratoses are a skin disease caused by long-term sun exposure, and their lesions have the potential to develop into squamous cell carcinoma. Treatments for actinic keratoses are sought for cosmetic reasons, for the relief of associated symptoms, or for the prevention of skin cancer development. Detectable lesions are often associated with alteration of the surrounding skin (field) where subclinical lesions might be present. The interventions available for the treatment of actinic keratoses include individual lesion-based (e.g. cryotherapy) or field-directed (e.g. topical) treatments. These might vary in terms of efficacy, safety, and cosmetic outcomes. To assess the effects of topical, oral, mechanical, and chemical interventions for actinic keratosis. We searched the following databases up to March 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2010), and LILACS (from 1982). We also searched trials registers, conference proceedings, and grey literature sources. Randomised controlled trials (RCTs) comparing the treatment of actinic keratoses with either placebo, vehicle, or another active therapy. At least two authors independently abstracted data, which included adverse events, and assessed the quality of evidence. We performed meta-analysis to calculate a weighted treatment effect across trials, and we expressed the results as risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes (e.g. participant complete clearance rates), and mean difference (MD) and 95% CI for continuous outcomes (e.g. mean reduction in lesion counts). We included 83 RCTs in this review, with a total of 10,036 participants. The RCTs covered 18 topical treatments, 1 oral treatment, 2 mechanical interventions, and 3 chemical interventions, including photodynamic therapy (PDT). Most of the studies lacked descriptions of some methodological details, such as the generation of the randomisation

78 FR 5128 - Amendment of Class E Airspace; Savoonga, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-24

...-0323; Airspace Docket No. 12-AAL-4] Amendment of Class E Airspace; Savoonga, AK AGENCY: Federal... Savoonga, AK, to accommodate aircraft using Area Navigation (RNAV) Global Positioning System (GPS) standard... modify controlled airspace at Savoonga, AK (77 FR 61304). Interested parties were invited to participate...

Actin Depolymerizing Factor (ADF/Cofilin) Enhances the Rate of Filament Turnover: Implication in Actin-based Motility

PubMed Central

Carlier, Marie-France; Laurent, Valérie; Santolini, Jérôme; Melki, Ronald; Didry, Dominique; Xia, Gui-Xian; Hong, Yan; Chua, Nam-Hai; Pantaloni, Dominique

1997-01-01

Actin-binding proteins of the actin depolymerizing factor (ADF)/cofilin family are thought to control actin-based motile processes. ADF1 from Arabidopsis thaliana appears to be a good model that is functionally similar to other members of the family. The function of ADF in actin dynamics has been examined using a combination of physical–chemical methods and actin-based motility assays, under physiological ionic conditions and at pH 7.8. ADF binds the ADPbound forms of G- or F-actin with an affinity two orders of magnitude higher than the ATP- or ADP-Pi– bound forms. A major property of ADF is its ability to enhance the in vitro turnover rate (treadmilling) of actin filaments to a value comparable to that observed in vivo in motile lamellipodia. ADF increases the rate of propulsion of Listeria monocytogenes in highly diluted, ADF-limited platelet extracts and shortens the actin tails. These effects are mediated by the participation of ADF in actin filament assembly, which results in a change in the kinetic parameters at the two ends of the actin filament. The kinetic effects of ADF are end specific and cannot be accounted for by filament severing. The main functionally relevant effect is a 25-fold increase in the rate of actin dissociation from the pointed ends, while the rate of dissociation from the barbed ends is unchanged. This large increase in the rate-limiting step of the monomer-polymer cycle at steady state is responsible for the increase in the rate of actin-based motile processes. In conclusion, the function of ADF is not to sequester G-actin. ADF uses ATP hydrolysis in actin assembly to enhance filament dynamics. PMID:9087445

Glutathione depletion triggers actin cytoskeleton changes via actin-binding proteins.

PubMed

Zepeta-Flores, Nahum; Valverde, Mahara; Lopez-Saavedra, Alejandro; Rojas, Emilio

2018-06-04

The importance of glutathione (GSH) in alternative cellular roles to the canonically proposed, were analyzed in a model unable to synthesize GSH. Gene expression analysis shows that the regulation of the actin cytoskeleton pathway is strongly impacted by the absence of GSH. To test this hypothesis, we evaluate the effect of GSH depletion via buthionine sulfoximine (5 and 12.5 mM) in human neuroblastoma MSN cells. In the present study, 70% of GSH reduction did not induce reactive oxygen species, lipoperoxidation, or cytotoxicity, which enabled us to evaluate the effect of glutathione in the absence of oxidative stress. The cells with decreasing GSH levels acquired morphology changes that depended on the actin cytoskeleton and not on tubulin. We evaluated the expression of three actin-binding proteins: thymosin β4, profilin and gelsolin, showing a reduced expression, both at gene and protein levels at 24 hours of treatment; however, this suppression disappears after 48 hours of treatment. These changes were sufficient to trigger the co-localization of the three proteins towards cytoplasmic projections. Our data confirm that a decrease in GSH in the absence of oxidative stress can transiently inhibit the actin binding proteins and that this stimulus is sufficient to induce changes in cellular morphology via the actin cytoskeleton.

Affimer proteins for F-actin: novel affinity reagents that label F-actin in live and fixed cells.

PubMed

Lopata, Anna; Hughes, Ruth; Tiede, Christian; Heissler, Sarah M; Sellers, James R; Knight, Peter J; Tomlinson, Darren; Peckham, Michelle

2018-04-26

Imaging the actin cytoskeleton in cells uses a wide range of approaches. Typically, a fluorescent derivative of the small cyclic peptide phalloidin is used to image F-actin in fixed cells. Lifeact and F-tractin are popular for imaging the cytoskeleton in live cells. Here we characterised novel affinity reagents called Affimers that specifically bind to F-actin in vitro to determine if they are suitable alternatives as eGFP-fusion proteins, to label actin in live cells, or for labeling F-actin in fixed cells. In vitro experiments showed that 3 out of the 4 Affimers (Affimers 6, 14 and 24) tested bind tightly to purified F-actin, and appear to have overlapping binding sites. As eGFP-fusion proteins, the same 3 Affimers label F-actin in live cells. FRAP experiments suggest that eGFP-Affimer 6 behaves most similarly to F-tractin and Lifeact. However, it does not colocalise with mCherry-actin in dynamic ruffles, and may preferentially bind stable actin filaments. All 4 Affimers label F-actin in methanol fixed cells, while only Affimer 14 labels F-actin after paraformaldehyde fixation. eGFP-Affimer 6 has potential for use in selectively imaging the stable actin cytoskeleton in live cells, while all 4 Affimers are strong alternatives to phalloidin for labelling F-actin in fixed cells.

78 FR 8962 - Establishment of Class E Airspace; Kasigluk, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-07

...-0952; Airspace Docket No. 12-AAL-6] Establishment of Class E Airspace; Kasigluk, AK AGENCY: Federal... at Kasigluk, AK, to accommodate aircraft using Area Navigation (RNAV) Global Positioning System (GPS... rulemaking to modify controlled airspace at Kasigluk, AK (77 FR 60660). Interested parties were invited to...

77 FR 6463 - Amendment of Class E Airspace; Kwigillingok, AK

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2012-02-08

...; Airspace Docket No. 11-AAL-18] Amendment of Class E Airspace; Kwigillingok, AK AGENCY: Federal Aviation..., Kwigillingok, AK. In that rule, errors were made in the geographic coordinates and legal description for... Airport, AK. Subsequent to publication, an error was found in the latitude coordinate for Kwigillingok...

76 FR 8626 - Revision of Class E Airspace; Shungnak, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-15

...-1104; Airspace Docket No. 10-AAL-19] Revision of Class E Airspace; Shungnak, AK AGENCY: Federal... Shungnak, AK, to accommodate amended Standard Instrument Approach Procedures (SIAPs) at the Shungnak..., Box 14, Anchorage, AK 99513-7587; telephone number (907) 271-5898; fax: (907) 271-2850; e- mail...

78 FR 45849 - Amendment of Class E Airspace; Gustavus, AK

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2013-07-30

...-0282; Airspace Docket No. 13-AAL-3] Amendment of Class E Airspace; Gustavus, AK AGENCY: Federal... Gustavus Airport, Gustavus, AK. Decommissioning of the Gustavus Nondirectional Radio Beacon (NDB) has made... Register a notice of proposed rulemaking (NPRM) to amend controlled airspace at Gustavus, AK (78 FR 31871...

77 FR 6 - Amendment of Class E Airspace; Kwigillingok, AK

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2012-01-03

...-0881; Airspace Docket No. 11-AAL-18] Amendment of Class E Airspace; Kwigillingok, AK AGENCY: Federal... Kwigillingok, AK. The revision of two standard instrument approach procedures at the Kwigillingok Airport has... airspace at Kwigillingok, AK (76 FR 54151). Interested parties were invited to participate in this...

75 FR 12676 - Establishment of Class E Airspace; Koyukuk, AK

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2010-03-17

...-0692; Airspace Docket No. 09-AAL-13] Establishment of Class E Airspace; Koyukuk, AK AGENCY: Federal... at Koyukuk, AK, to accommodate new Area Navigation (RNAV) Standard Instrument Approach Procedures...-538G, Federal Aviation Administration, 222 West 7th Avenue, Box 14, Anchorage, AK 99513-7587; telephone...

75 FR 12677 - Establishment of Class E Airspace; Shaktoolik, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-17

...-0142; Airspace Docket No. 09-AAL-2] Establishment of Class E Airspace; Shaktoolik, AK AGENCY: Federal... at Shaktoolik, AK, to accommodate new Area Navigation (RNAV) Standard Instrument Approach Procedures...: Gary Rolf, AAL-538G, Federal Aviation Administration, 222 West 7th Avenue, Box 14, Anchorage, AK 99513...

Cytoskeletal actin dynamics shape a ramifying actin network underpinning immunological synapse formation

PubMed Central

Fritzsche, Marco; Fernandes, Ricardo A.; Chang, Veronica T.; Colin-York, Huw; Clausen, Mathias P.; Felce, James H.; Galiani, Silvia; Erlenkämper, Christoph; Santos, Ana M.; Heddleston, John M.; Pedroza-Pacheco, Isabela; Waithe, Dominic; de la Serna, Jorge Bernardino; Lagerholm, B. Christoffer; Liu, Tsung-li; Chew, Teng-Leong; Betzig, Eric; Davis, Simon J.; Eggeling, Christian

2017-01-01

T cell activation and especially trafficking of T cell receptor microclusters during immunological synapse formation are widely thought to rely on cytoskeletal remodeling. However, important details on the involvement of actin in the latter transport processes are missing. Using a suite of advanced optical microscopes to analyze resting and activated T cells, we show that, following contact formation with activating surfaces, these cells sequentially rearrange their cortical actin across the entire cell, creating a previously unreported ramifying actin network above the immunological synapse. This network shows all the characteristics of an inward-growing transportation network and its dynamics correlating with T cell receptor rearrangements. This actin reorganization is accompanied by an increase in the nanoscale actin meshwork size and the dynamic adjustment of the turnover times and filament lengths of two differently sized filamentous actin populations, wherein formin-mediated long actin filaments support a very flat and stiff contact at the immunological synapse interface. The initiation of immunological synapse formation, as highlighted by calcium release, requires markedly little contact with activating surfaces and no cytoskeletal rearrangements. Our work suggests that incipient signaling in T cells initiates global cytoskeletal rearrangements across the whole cell, including a stiffening process for possibly mechanically supporting contact formation at the immunological synapse interface as well as a central ramified transportation network apparently directed at the consolidation of the contact and the delivery of effector functions. PMID:28691087

75 FR 32269 - Revision of Class E Airspace; Wainwright, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-08

...-0080; Airspace Docket No. 10-AAL-2] Revision of Class E Airspace; Wainwright, AK AGENCY: Federal... Wainwright, AK, to accommodate amended Standard Instrument Approach Procedures (SIAPs), and one new Obstacle... Administration, 222 West 7th Avenue, Box 14, Anchorage, AK 99513-7587; telephone number (907) 271-5898; fax: (907...

76 FR 43823 - Revision of Class E Airspace; Yakutat, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-22

...-0244 Airspace Docket No. 11-AAL-05] Revision of Class E Airspace; Yakutat, AK AGENCY: Federal Aviation... Airport, Yakutat, AK. The amendment of eight Standard Instrument Approach Procedures (SIAPs) has made this... INFORMATION CONTACT: Martha Dunn, Federal Aviation Administration, 222 West 7th Avenue, Box 14, Anchorage, AK...

Pharmacokinetics and safety of imiquimod 5% cream in the treatment of actinic keratoses of the face, scalp, or hands and arms.

PubMed

Harrison, Lester I; Skinner, Shari L; Marbury, Thomas C; Owens, Mary L; Kurup, Sarala; McKane, Scott; Greene, Robert J

2004-06-01

The safety and efficacy of imiquimod 5% cream is being evaluated for the treatment of dysplastic lesions of the epidermis (actinic keratoses, AK). The objective of this clinical study was to describe the pharmacokinetics and safety of topical imiquimod during multiple dosing of AK subjects. A total of 58 adult subjects with 5 to 20 AK lesions at the treatment site applied imiquimod cream three times per week for up to 16 weeks as follows: 12 males and 11 females applied 12.5 mg imiquimod to the face; 11 males applied 25 mg to the entire balding area of the scalp; and 12 males and 12 females applied 75 mg to both hands and forearms. Pharmacokinetics and safety were assessed after the first and last doses, as well as biweekly. Imiquimod and its metabolites were measured in the serum and urine using sensitive liquid chromatography/mass spectrometry methods. Less than 0.6% of the applied doses was recovered in the urine of all subjects. Serum imiquimod levels were low, reflecting minimal dermal absorption, and increased with dose, although not proportionally. Peak levels at the end of dosing were 0.1, 0.2, and 1.6 ng/ml for the face, scalp, and hands/arms groups, respectively. A two- to fourfold accumulation was seen at the end of dosing. Local application site reactions were the most common adverse event, reported by approximately 50% of the subjects in each treatment group. The small number of systemic adverse events, including 'flu-like symptoms, were mostly mild and did not show a dose response. Thus, minimal systemic absorption and good safety margins for topical imiquimod were seen in AK subjects with doses as high as 75 mg three times per week for 16 weeks.

76 FR 8627 - Revision of Class E Airspace; Platinum, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-15

...-1105; Airspace Docket No. 10-AAL-20] Revision of Class E Airspace; Platinum, AK AGENCY: Federal... Platinum, AK, to accommodate the addition of a Standard Instrument Approach Procedure (SIAP), at the... 7th Avenue, Box 14, Anchorage, AK 99513-7587; telephone number (907) 271-5898; fax: (907) 271-2850; e...

76 FR 8625 - Revision of Class E Airspace; Savoonga, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-15

...-1103 Airspace Docket No. 10-AAL-18] Revision of Class E Airspace; Savoonga, AK AGENCY: Federal Aviation... Airport, Savoonga, AK. The amendment of three Standard Instrument Approach Procedures (SIAPs) plus the... Administration, 222 West 7th Avenue, Box 14, Anchorage, AK 99513-7587; telephone number (907) 271-5898; fax: (907...

77 FR 5 - Amendment of Class E Airspace; Kipnuk, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-03

...-0866; Airspace Docket No. 11-AAL-15] Amendment of Class E Airspace; Kipnuk, AK AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action modifies Class E airspace at Kipnuk, AK. The... a notice of proposed rulemaking (NPRM) to amend controlled airspace at Kipnuk, AK (76 FR 54149...

75 FR 32271 - Revision of Class E Airspace; Nenana, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-08

...-0081; Airspace Docket No. 10-AAL-3] Revision of Class E Airspace; Nenana, AK AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action revises Class E airspace at Nenana, AK, to..., Federal Aviation Administration, 222 West 7th Avenue, Box 14, Anchorage, AK 99513-7587; telephone number...

75 FR 12679 - Revision of Class E Airspace; Iliamna, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-17

...-1036; Airspace Docket No. 09-AAL-17] Revision of Class E Airspace; Iliamna, AK AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action revises Class E airspace at Iliamna, AK, to..., Federal Aviation Administration, 222 West 7th Avenue, Box 14, Anchorage, AK 99513-7587; telephone number...

75 FR 33165 - Revision of Class E Airspace; Galena, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-11

...-0299; Airspace Docket No. 10-AAL-9] Revision of Class E Airspace; Galena, AK AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final Rule. SUMMARY: This action revises Class E airspace at Galena, AK, to...-538G, Federal Aviation Administration, 222 West 7th Avenue, Box 14, Anchorage, AK 99513-7587; telephone...

Mechanism of Actin-Based Motility

NASA Astrophysics Data System (ADS)

Pantaloni, Dominique; Le Clainche, Christophe; Carlier, Marie-France

2001-05-01

Spatially controlled polymerization of actin is at the origin of cell motility and is responsible for the formation of cellular protrusions like lamellipodia. The pathogens Listeria monocytogenes and Shigella flexneri, which undergo actin-based propulsion, are acknowledged models of the leading edge of lamellipodia. Actin-based motility of the bacteria or of functionalized microspheres can be reconstituted in vitro from only five pure proteins. Movement results from the regulated site-directed treadmilling of actin filaments, consistent with observations of actin dynamics in living motile cells and with the biochemical properties of the components of the synthetic motility medium.

Actin filaments as tension sensors.

PubMed

Galkin, Vitold E; Orlova, Albina; Egelman, Edward H

2012-02-07

The field of mechanobiology has witnessed an explosive growth over the past several years as interest has greatly increased in understanding how mechanical forces are transduced by cells and how cells migrate, adhere and generate traction. Actin, a highly abundant and anomalously conserved protein, plays a large role in forming the dynamic cytoskeleton that is so essential for cell form, motility and mechanosensitivity. While the actin filament (F-actin) has been viewed as dynamic in terms of polymerization and depolymerization, new results suggest that F-actin itself may function as a highly dynamic tension sensor. This property may help explain the unusual conservation of actin's sequence, as well as shed further light on actin's essential role in structures from sarcomeres to stress fibers. Copyright © 2012 Elsevier Ltd. All rights reserved.

75 FR 62458 - Revision of Class E Airspace; Tanana, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-12

...-0588 Airspace Docket No. 10-AAL-16] Revision of Class E Airspace; Tanana, AK AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action revises Class E airspace at Tanana, AK. The... West 7th Avenue, Box 14, Anchorage, AK 99513-7587; telephone number (907) 271-5898; fax: (907) 271-2850...

76 FR 8624 - Revision of Class E Airspace; Barrow, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-15

...-0722 Airspace Docket No. 10-AAL-17] Revision of Class E Airspace; Barrow, AK AGENCY: Federal Aviation... Rogers Memorial Airport in Barrow, AK, in order to accommodate the amendment of five Standard Instrument... Administration, 222 West 7th Avenue, Box 14, Anchorage, AK 99513-7587; telephone number (907) 271-5898; fax: (907...

76 FR 66178 - Revision of Class E Airspace; Umiat, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-26

...-0750; Airspace Docket No. 11-AAL-08] Revision of Class E Airspace; Umiat, AK AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action revises Class E airspace at Umiat, AK, due to...-538G, Federal Aviation Administration, 222 West 7th Avenue, Box 14, Anchorage, AK 99513-7587; telephone...

75 FR 32272 - Revision of Class E Airspace; Kaltag, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-08

...-0082; Airspace Docket No. 10-AAL-4] Revision of Class E Airspace; Kaltag, AK AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action revises Class E airspace at Kaltag, AK, to..., Anchorage, AK 99513-7587; telephone number (907) 271-5898; fax: (907) 271-2850; e-mail: [email protected

Interactions between G-actin and myosin subfragment 1: immunochemical probing of the NH2-terminal segment on actin.

PubMed

DasGupta, G; White, J; Cheung, P; Reisler, E

1990-09-11

The role of the N-terminal segment of actin in myosin-induced polymerization of G-actin was studied by using peptide antibodies directed against the first seven N-terminal residues of alpha-skeletal actin. Light scattering, fluorescence, and analytical ultracentrifugation experiments showed that the Fab fragments of these antibodies inhibited the polymerization of G-actin by myosin subfragment 1 (S-1) by inhibiting the binding of these proteins to each other. Fluorescence measurements using actin labeled with pyrenyliodoacetamide revealed that Fab inhibited the initial step in the binding of S-1 to G-actin. It is deduced from these results and from other literature data that the initial contact between G-actin and S-1 involves residues 1-7 on actin and residues 633-642 on the S-1 heavy chain. This interaction appears to be of major importance for the binding of S-1 and G-actin. The presence of additional myosin contact sites on G-actin was indicated by concentration-dependent recovery of S-1 binding to G-actin without displacement of Fab. The reduced Fab inhibition of S-1 binding to polymerizing and polymerized actin is consistent with the tightening of acto-S-1 binding at these sites or the creation of new sites upon formation of F-actin.

Computational model of polarized actin cables and cytokinetic actin ring formation in budding yeast

PubMed Central

Tang, Haosu; Bidone, Tamara C.

2015-01-01

The budding yeast actin cables and contractile ring are important for polarized growth and division, revealing basic aspects of cytoskeletal function. To study these formin-nucleated structures, we built a 3D computational model with actin filaments represented as beads connected by springs. Polymerization by formins at the bud tip and bud neck, crosslinking, severing, and myosin pulling, are included. Parameter values were estimated from prior experiments. The model generates actin cable structures and dynamics similar to those of wild type and formin deletion mutant cells. Simulations with increased polymerization rate result in long, wavy cables. Simulated pulling by type V myosin stretches actin cables. Increasing the affinity of actin filaments for the bud neck together with reduced myosin V pulling promotes the formation of a bundle of antiparallel filaments at the bud neck, which we suggest as a model for the assembly of actin filaments to the contractile ring. PMID:26538307

78 FR 22190 - Modification of Area Navigation (RNAV) Route T-266; AK

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-15

...; AK AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action... modifying RNAV route T-266 in Alaska. T-266 is currently defined by the Coghland Island, AK, NDB, the Fredericks Point, AK, NDB and the Annette Island, AK, VOR/DME. The Annette Island VOR/DME remains as one end...

76 FR 54152 - Proposed Amendment of Class E Airspace Galbraith Lake, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-31

..., AK [Revised] Galbraith Lake Airport, AK (Lat. 68[deg]28'47'' N., long. 149[deg]29'24'' W) That...-0865; Airspace Docket No. 11-AAL-14] Proposed Amendment of Class E Airspace Galbraith Lake, AK AGENCY... action proposes to amend Class E airspace at Galbraith Lake AK. The creation of two special instrument...

Role of gelsolin interaction with actin in regulation and creation of actin nuclei in chemotactic peptide activated polymorphonuclear neutrophils.

PubMed Central

Deaton, J D; Guerrero, T; Howard, T H

1992-01-01

In vitro Ca++ activates gelsolin to sever F-actin and form a gelsolin-actin (GA) complex at the+end of F-actin that is not dissociated by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) but is separated by EGTA+PIP/PIP2. The gelsolin blocks the+end on the actin filament, but the-end of the filament can still initiate actin polymerization. In thrombin activated platelets, evidence suggests that severing of F-actin by gelsolin increases GA complex, creates one-end actin nucleus and one cryptic+end actin nucleus per cut, and then dissociates to yield free+ends to nucleate rapid actin assembly. We examined the role of F-actin severing in creation and regulation of nuclei and polymerization in polymorphonuclear neutrophils (PMNs). At 2-s intervals after formyl peptide (FMLP) activation of endotoxin free (ETF) PMNs, change in GA complex was correlated with change in+end actin nuclei,-end actin nuclei, and F-actin content. GA complex was quantitated by electrophoretograms of proteins absorbed by antigelsolin from cells lysed in 10 mM EGTA,+end actin nuclei as cytochalasin (CD) sensitive and-end actin nuclei as CD insensitive increases in G-pyrenyl actin polymerization rates induced by the same PMNs, and F-actin content by NBDphallacidin binding to fixed cells. Thirty three percent of gelsolin was in GA complex in basal ETF PMNs; from 2-6 s, GA complexes dissociate (low = 15% at 10 s) and sequentially+end nuclei and F-actin content and then-end nuclei increase to a maximum at 10 s. At > s GA complex increase toward basal and + end nuclei and F-actin content returned toward basal. These kinetic data show gelsolin regulates availability of + end nuclei and actin polymerization in FMLP. However, absence of an initial increase in GA complex or - end nucleating activity shows FMLP activation does not cause gelsolin to sever F- or to bind G-actin to create cryptic + end nuclei in PMNs; the results suggest the + nucleus formation is gelsolin

Role of gelsolin interaction with actin in regulation and creation of actin nuclei in chemotactic peptide activated polymorphonuclear neutrophils.

PubMed

Deaton, J D; Guerrero, T; Howard, T H

1992-12-01

In vitro Ca++ activates gelsolin to sever F-actin and form a gelsolin-actin (GA) complex at the+end of F-actin that is not dissociated by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) but is separated by EGTA+PIP/PIP2. The gelsolin blocks the+end on the actin filament, but the-end of the filament can still initiate actin polymerization. In thrombin activated platelets, evidence suggests that severing of F-actin by gelsolin increases GA complex, creates one-end actin nucleus and one cryptic+end actin nucleus per cut, and then dissociates to yield free+ends to nucleate rapid actin assembly. We examined the role of F-actin severing in creation and regulation of nuclei and polymerization in polymorphonuclear neutrophils (PMNs). At 2-s intervals after formyl peptide (FMLP) activation of endotoxin free (ETF) PMNs, change in GA complex was correlated with change in+end actin nuclei,-end actin nuclei, and F-actin content. GA complex was quantitated by electrophoretograms of proteins absorbed by antigelsolin from cells lysed in 10 mM EGTA,+end actin nuclei as cytochalasin (CD) sensitive and-end actin nuclei as CD insensitive increases in G-pyrenyl actin polymerization rates induced by the same PMNs, and F-actin content by NBDphallacidin binding to fixed cells. Thirty three percent of gelsolin was in GA complex in basal ETF PMNs; from 2-6 s, GA complexes dissociate (low = 15% at 10 s) and sequentially+end nuclei and F-actin content and then-end nuclei increase to a maximum at 10 s. At > s GA complex increase toward basal and + end nuclei and F-actin content returned toward basal. These kinetic data show gelsolin regulates availability of + end nuclei and actin polymerization in FMLP. However, absence of an initial increase in GA complex or - end nucleating activity shows FMLP activation does not cause gelsolin to sever F- or to bind G-actin to create cryptic + end nuclei in PMNs; the results suggest the + nucleus formation is gelsolin

Clinical pharmacokinetic study and sensitive effect of AK-2123

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo Chuan Huan; Bao Yun Hua

1994-06-15

The pharmacokinetic parameters of a radiosensitizer, AK-2123 (a nitrotriazole deriv.) given to 10 lung cancer patients are represented and its sensitizing effect is evaluated. The diagnosis was confirmed radiologically and pathologically. Seven patients were diagnosed with squamous cell cancer, two had adenocarcinoma, and one had nonsquamous cell lung cancer. AK-2123 was administered orally twice a week. The total dose per patient was 12.8-15.75 g. Radiotherapy was delivered 3 h after AK-2123 administration, 2 Gy per fraction. Blood samples were taken from the ear at 1, 3, 6, 9, 12, and 24 h after AK-2123 administration. The concentration of AK-2123 inmore » plasma was measured by HPLC. The C[sub m] (maximum concentration of AK-2123 averaging from 10 patients) was 27.75 [mu]g/mL, ranging 22.62-39.97 [mu]g/mL, T[sub m] (the time of getting C[sub m]) 3 h. The data of the drug fitted a two-compartment open model. The mean parameters of these cases were: rate constant K12 0.1658, K21 0.0671, Ke 0.0254, h[sup [minus]1]; apparent volumes of distribution V[sub 1] 18.6154, V[sub 2] 51.2317, L; biological half life T[sub 1]2a 1.0863, T[sub 1]2[alpha] 2.7546, T[sub 1]2[beta] 35.2064 h. The response to the treatment: CR four cases, PR four cases, NC two cases. So, AK-2123 may be a promising radiosensitizer. 5 refs., 4 figs., 2 tabs.« less

Arp2/3 complex–dependent actin networks constrain myosin II function in driving retrograde actin flow

PubMed Central

Yang, Qing; Zhang, Xiao-Feng; Pollard, Thomas D.

2012-01-01

The Arp2/3 complex nucleates actin filaments to generate networks at the leading edge of motile cells. Nonmuscle myosin II produces contractile forces involved in driving actin network translocation. We inhibited the Arp2/3 complex and/or myosin II with small molecules to investigate their respective functions in neuronal growth cone actin dynamics. Inhibition of the Arp2/3 complex with CK666 reduced barbed end actin assembly site density at the leading edge, disrupted actin veils, and resulted in veil retraction. Strikingly, retrograde actin flow rates increased with Arp2/3 complex inhibition; however, when myosin II activity was blocked, Arp2/3 complex inhibition now resulted in slowing of retrograde actin flow and veils no longer retracted. Retrograde flow rate increases induced by Arp2/3 complex inhibition were independent of Rho kinase activity. These results provide evidence that, although the Arp2/3 complex and myosin II are spatially segregated, actin networks assembled by the Arp2/3 complex can restrict myosin II–dependent contractility with consequent effects on growth cone motility. PMID:22711700

A Second Las17 Monomeric Actin-Binding Motif Functions in Arp2/3-Dependent Actin Polymerization During Endocytosis

PubMed Central

Feliciano, Daniel; Tolsma, Thomas O.; Farrell, Kristen B.; Aradi, Al; Di Pietro, Santiago M.

2018-01-01

During clathrin-mediated endocytosis (CME), actin assembly provides force to drive vesicle internalization. Members of the Wiskott–Aldrich syndrome protein (WASP) family play a fundamental role stimulating actin assembly. WASP family proteins contain a WH2 motif that binds globular actin (G-actin) and a central-acidic motif that binds the Arp2/3 complex, thus promoting the formation of branched actin filaments. Yeast WASP (Las17) is the strongest of five factors promoting Arp2/3-dependent actin polymerization during CME. It was suggested that this strong activity may be caused by a putative second G-actin-binding motif in Las17. Here, we describe the in vitro and in vivo characterization of such Las17 G-actin-binding motif (LGM) and its dependence on a group of conserved arginine residues. Using the yeast two-hybrid system, GST-pulldown, fluorescence polarization and pyrene-actin polymerization assays, we show that LGM binds G-actin and is necessary for normal Arp2/3-mediated actin polymerization in vitro. Live-cell fluorescence microscopy experiments demonstrate that LGM is required for normal dynamics of actin polymerization during CME. Further, LGM is necessary for normal dynamics of endocytic machinery components that are recruited at early, intermediate and late stages of endocytosis, as well as for optimal endocytosis of native CME cargo. Both in vitro and in vivo experiments show that LGM has relatively lower potency compared to the previously known Las17 G-actin-binding motif, WH2. These results establish a second G-actin-binding motif in Las17 and advance our knowledge on the mechanism of actin assembly during CME. PMID:25615019

United States Food and Drug Administration Product Label Changes

PubMed Central

Sung, Julie C.; Stein-Gold, Linda; Goldenberg, Gary

2017-01-01

Once a drug has been approved by the United States Food and Drug Administration and is on the market, the Food and Drug Administration communicates new safety information through product label changes. Most of these label changes occur after a spontaneous report to either the drug manufacturing companies or the Food and Drug Administration MedWatch program. As a result, 400 to 500 label changes occur every year. Actinic keratosis treatments exemplify the commonality of label changes throughout the postmarket course of a drug. Diclofenac gel, 5-fluorouracil cream, imiquimod, and ingenol mebutate are examples of actinic keratosis treatments that have all undergone at least one label revision. With the current system of spontaneous reports leading to numerous label changes, each occurrence does not necessarily signify a radical change in the safety of a drug. PMID:28367259

United States Food and Drug Administration Product Label Changes

PubMed Central

Sung, Julie C.; Stein-Gold, Linda; Goldenberg, Gary

2016-01-01

Once a drug has been approved by the United States Food and Drug Administration and is on the market, the Food and Drug Administration communicates new safety information through product label changes. Most of these label changes occur after a spontaneous report to either the drug manufacturing companies or the Food and Drug Administration MedWatch program. As a result, 400 to 500 label changes occur every year. Actinic keratosis treatments exemplify the commonality of label changes throughout the postmarket course of a drug. Diclofenac gel, 5-fluorouracil cream, imiquimod, and ingenol mebutate are examples of actinic keratosis treatments that have all undergone at least one label revision. With the current system of spontaneous reports leading to numerous label changes, each occurrence does not necessarily signify a radical change in the safety of a drug. PMID:26962391

75 FR 38753 - Proposed Revision of Class E Airspace; Tanana, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-06

... E Airspace; Tanana, AK AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed rulemaking (NPRM). SUMMARY: This action proposes to revise Class E airspace at Tanana, AK. The..., Anchorage, AK 99513-7587. FOR FURTHER INFORMATION CONTACT: Gary Rolf, Federal Aviation Administration, 222...

Fascin regulates nuclear actin during Drosophila oogenesis

PubMed Central

Kelpsch, Daniel J.; Groen, Christopher M.; Fagan, Tiffany N.; Sudhir, Sweta; Tootle, Tina L.

2016-01-01

Drosophila oogenesis provides a developmental system with which to study nuclear actin. During Stages 5–9, nuclear actin levels are high in the oocyte and exhibit variation within the nurse cells. Cofilin and Profilin, which regulate the nuclear import and export of actin, also localize to the nuclei. Expression of GFP-tagged Actin results in nuclear actin rod formation. These findings indicate that nuclear actin must be tightly regulated during oogenesis. One factor mediating this regulation is Fascin. Overexpression of Fascin enhances nuclear GFP-Actin rod formation, and Fascin colocalizes with the rods. Loss of Fascin reduces, whereas overexpression of Fascin increases, the frequency of nurse cells with high levels of nuclear actin, but neither alters the overall nuclear level of actin within the ovary. These data suggest that Fascin regulates the ability of specific cells to accumulate nuclear actin. Evidence indicates that Fascin positively regulates nuclear actin through Cofilin. Loss of Fascin results in decreased nuclear Cofilin. In addition, Fascin and Cofilin genetically interact, as double heterozygotes exhibit a reduction in the number of nurse cells with high nuclear actin levels. These findings are likely applicable beyond Drosophila follicle development, as the localization and functions of Fascin and the mechanisms regulating nuclear actin are widely conserved. PMID:27535426

46 CFR 7.180 - Kotzebue Sound, AK.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Kotzebue Sound, AK. 7.180 Section 7.180 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.180 Kotzebue Sound, AK. A line drawn from Cape Espenberg Light to latitude 66°52′ N. longitude 163°28′ W.; and...

46 CFR 7.180 - Kotzebue Sound, AK.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 1 2013-10-01 2013-10-01 false Kotzebue Sound, AK. 7.180 Section 7.180 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.180 Kotzebue Sound, AK. A line drawn from Cape Espenberg Light to latitude 66°52′ N. longitude 163°28′ W.; and...

46 CFR 7.180 - Kotzebue Sound, AK.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 1 2014-10-01 2014-10-01 false Kotzebue Sound, AK. 7.180 Section 7.180 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.180 Kotzebue Sound, AK. A line drawn from Cape Espenberg Light to latitude 66°52′ N. longitude 163°28′ W.; and...

46 CFR 7.180 - Kotzebue Sound, AK.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 1 2012-10-01 2012-10-01 false Kotzebue Sound, AK. 7.180 Section 7.180 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.180 Kotzebue Sound, AK. A line drawn from Cape Espenberg Light to latitude 66°52′ N. longitude 163°28′ W.; and...

46 CFR 7.180 - Kotzebue Sound, AK.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Kotzebue Sound, AK. 7.180 Section 7.180 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Alaska § 7.180 Kotzebue Sound, AK. A line drawn from Cape Espenberg Light to latitude 66°52′ N. longitude 163°28′ W.; and...

Geometrical Determinants of Neuronal Actin Waves.

PubMed

Tomba, Caterina; Braïni, Céline; Bugnicourt, Ghislain; Cohen, Floriane; Friedrich, Benjamin M; Gov, Nir S; Villard, Catherine

2017-01-01

Hippocampal neurons produce in their early stages of growth propagative, actin-rich dynamical structures called actin waves. The directional motion of actin waves from the soma to the tip of neuronal extensions has been associated with net forward growth, and ultimately with the specification of neurites into axon and dendrites. Here, geometrical cues are used to control actin wave dynamics by constraining neurons on adhesive stripes of various widths. A key observable, the average time between the production of consecutive actin waves, or mean inter-wave interval (IWI), was identified. It scales with the neurite width, and more precisely with the width of the proximal segment close to the soma. In addition, the IWI is independent of the total number of neurites. These two results suggest a mechanistic model of actin wave production, by which the material conveyed by actin waves is assembled in the soma until it reaches the threshold leading to the initiation and propagation of a new actin wave. Based on these observations, we formulate a predictive theoretical description of actin wave-driven neuronal growth and polarization, which consistently accounts for different sets of experiments.

Geometrical Determinants of Neuronal Actin Waves

PubMed Central

Tomba, Caterina; Braïni, Céline; Bugnicourt, Ghislain; Cohen, Floriane; Friedrich, Benjamin M.; Gov, Nir S.; Villard, Catherine

2017-01-01

Hippocampal neurons produce in their early stages of growth propagative, actin-rich dynamical structures called actin waves. The directional motion of actin waves from the soma to the tip of neuronal extensions has been associated with net forward growth, and ultimately with the specification of neurites into axon and dendrites. Here, geometrical cues are used to control actin wave dynamics by constraining neurons on adhesive stripes of various widths. A key observable, the average time between the production of consecutive actin waves, or mean inter-wave interval (IWI), was identified. It scales with the neurite width, and more precisely with the width of the proximal segment close to the soma. In addition, the IWI is independent of the total number of neurites. These two results suggest a mechanistic model of actin wave production, by which the material conveyed by actin waves is assembled in the soma until it reaches the threshold leading to the initiation and propagation of a new actin wave. Based on these observations, we formulate a predictive theoretical description of actin wave-driven neuronal growth and polarization, which consistently accounts for different sets of experiments. PMID:28424590

Basal Cell Carcinoma Arising within Seborrheic Keratosis

PubMed Central

Yurdakul, Cüneyt; Güçer, Hasan; Sehitoglu, Ibrahim

2014-01-01

Malignant tumour development within a seborrheic keratosis (SK) is extremely rare. Though the most commonly developed malignant tumour is the basal cell carcinoma (BCC), other tumour types have also been reported in literature. Herein, we will report a superficial type BCC case developed within SK localized in hairy skin of a 78-year-old female patient. In immunohistochemical evaluation, diffuse positive staining with CK19 and over-expression in p53 compared with non-neoplastic areas were determined in neoplastic basaloid islands. It is always not easy to differentiate especially superficial type BCC cases from non-neoplastic epithelium of SK with histopathological evaluation. As far as this reason we believe that in difficult differentiation of these 2 lesions, in order to show the differentiation in basal epithelium, immunohistochemical evaluation may be helpful. PMID:25177624

78 FR 65237 - Proposed Establishment of Class E Airspace; Central, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

...-0017; Airspace Docket No. 13-AAL-1] Proposed Establishment of Class E Airspace; Central, AK AGENCY... action proposes to establish Class E airspace at Central Airport, Central, AK. Controlled airspace is... of aircraft operations at Central Airport, Central, AK. DATES: Comments must be received on or before...

78 FR 59806 - Establishment of Class E Airspace; White Mountain, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-30

...-1185; Airspace Docket No. 12-AAL-8] Establishment of Class E Airspace; White Mountain, AK AGENCY... airspace at White Mountain Airport, White Mountain, AK, to accommodate aircraft using new Area Navigation..., Airport, White Mountain, AK (77 FR 75598). Interested parties were invited to participate in this...

Decolorization of sulfonated azo dye Metanil Yellow by newly isolated bacterial strains: Bacillus sp. strain AK1 and Lysinibacillus sp. strain AK2.

PubMed

Anjaneya, O; Souche, S Yogesh; Santoshkumar, M; Karegoudar, T B

2011-06-15

Two different bacterial strains capable of decolorizing a highly water soluble azo dye Metanil Yellow were isolated from dye contaminated soil sample collected from Atul Dyeing Industry, Bellary, India. The individual bacterial strains Bacillus sp. AK1 and Lysinibacillus sp. AK2 decolorized Metanil Yellow (200 mg L(-1)) completely within 27 and 12h respectively. Various parameters like pH, temperature, NaCl and initial dye concentrations were optimized to develop an economically feasible decolorization process. The maximum concentration of Metanil Yellow (1000 mg L(-1)) was decolorized by strains AK2 and AK1 within 78 and 84 h respectively. These strains could decolorize Metanil Yellow over a broad pH range 5.5-9.0; the optimum pH was 7.2. The decolorization of Metanil Yellow was most efficient at 40°C and confirmed by UV-visible spectroscopy, TLC, HPLC and GC/MS analysis. Further, both the strains showed the involvement of azoreductase in the decolorization process. Phytotoxicity studies of catabolic products of Metanil Yellow on the seeds of chick pea and pigeon pea revealed much reduction in the toxicity of metabolites as compared to the parent dye. These results indicating the effectiveness of strains AK1 and AK2 for the treatment of textile effluents containing azo dyes. Copyright © 2011 Elsevier B.V. All rights reserved.

Bacterial Actins.

PubMed

Izoré, Thierry; van den Ent, Fusinita

2017-01-01

A diverse set of protein polymers, structurally related to actin filaments contributes to the organization of bacterial cells as cytomotive or cytoskeletal filaments. This chapter describes actin homologs encoded by bacterial chromosomes. MamK filaments, unique to magnetotactic bacteria, help establishing magnetic biological compasses by interacting with magnetosomes. Magnetosomes are intracellular membrane invaginations containing biomineralized crystals of iron oxide that are positioned by MamK along the long-axis of the cell. FtsA is widespread across bacteria and it is one of the earliest components of the divisome to arrive at midcell, where it anchors the cell division machinery to the membrane. FtsA binds directly to FtsZ filaments and to the membrane through its C-terminus. FtsA shows altered domain architecture when compared to the canonical actin fold. FtsA's subdomain 1C replaces subdomain 1B of other members of the actin family and is located on the opposite side of the molecule. Nevertheless, when FtsA assembles into protofilaments, the protofilament structure is preserved, as subdomain 1C replaces subdomain IB of the following subunit in a canonical actin filament. MreB has an essential role in shape-maintenance of most rod-shaped bacteria. Unusually, MreB filaments assemble from two protofilaments in a flat and antiparallel arrangement. This non-polar architecture implies that both MreB filament ends are structurally identical. MreB filaments bind directly to membranes where they interact with both cytosolic and membrane proteins, thereby forming a key component of the elongasome. MreB filaments in cells are short and dynamic, moving around the long axis of rod-shaped cells, sensing curvature of the membrane and being implicated in peptidoglycan synthesis.

78 FR 65238 - Proposed Establishment of Class E Airspace; Eagle, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

...-0777; Airspace Docket No. 12-AAL-16] Proposed Establishment of Class E Airspace; Eagle, AK AGENCY... action proposes to establish Class E airspace at Eagle Airport, Eagle, AK. Controlled airspace is... management of aircraft operations at Eagle Airport, Eagle, AK. DATES: Comments must be received on or before...

76 FR 49387 - Proposed Amendment of Class E Airspace; Umiat, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-10

...-0750 Airspace Docket No. 11-AAL-08] Proposed Amendment of Class E Airspace; Umiat, AK AGENCY: Federal... proposes to revise Class E airspace at Umiat, AK. The cancellation of two special Instrument Approach... Operations, Federal Aviation Administration, 222 West 7th Avenue, Box 14, Anchorage, AK 99513-7587. FOR...

75 FR 77573 - Proposed Revision of Class E Airspace; Shungnak, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-13

...-1104 Airspace Docket No. 10-AAL-19] Proposed Revision of Class E Airspace; Shungnak, AK AGENCY: Federal... proposes to revise Class E airspace at Shungnak, AK. The amendment of Standard Instrument Approach... Administration, 222 West 7th Avenue, Box 14, Anchorage, AK 99513-7587. FOR FURTHER INFORMATION CONTACT: Martha...

78 FR 69787 - Proposed Modification of Class E Airspace; Sitka, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-21

...-0921; Airspace Docket No. 13-AAL-4] Proposed Modification of Class E Airspace; Sitka, AK AGENCY... rulemaking (NPRM). SUMMARY: This action proposes to modify Class E airspace at Sitka, AK, to [[Page 69788... Gutierrez, AK. After review of the airspace, the FAAs Western Terminal Products Office found modification of...

77 FR 6 - Amendment of Class E Airspace; Galbraith Lake, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-03

...-0865; Airspace Docket No. 11-AAL-14] Amendment of Class E Airspace; Galbraith Lake, AK AGENCY: Federal... Galbraith Lake, AK. The creation of two standard instrument approach procedures at the Galbraith Lake... airspace at Galbraith Lake, AK (76 FR 54152). Interested parties were invited to participate in this...

Surface-induced polymerization of actin.

PubMed Central

Renault, A; Lenne, P F; Zakri, C; Aradian, A; Vénien-Bryan, C; Amblard, F

1999-01-01

Living cells contain a very large amount of membrane surface area, which potentially influences the direction, the kinetics, and the localization of biochemical reactions. This paper quantitatively evaluates the possibility that a lipid monolayer can adsorb actin from a nonpolymerizing solution, induce its polymerization, and form a 2D network of individual actin filaments, in conditions that forbid bulk polymerization. G- and F-actin solutions were studied beneath saturated Langmuir monolayers containing phosphatidylcholine (PC, neutral) and stearylamine (SA, a positively charged surfactant) at PC:SA = 3:1 molar ratio. Ellipsometry, tensiometry, shear elastic measurements, electron microscopy, and dark-field light microscopy were used to characterize the adsorption kinetics and the interfacial polymerization of actin. In all cases studied, actin follows a monoexponential reaction-limited adsorption with similar time constants (approximately 10(3) s). At a longer time scale the shear elasticity of the monomeric actin adsorbate increases only in the presence of lipids, to a 2D shear elastic modulus of mu approximately 30 mN/m, indicating the formation of a structure coupled to the monolayer. Electron microscopy shows the formation of a 2D network of actin filaments at the PC:SA surface, and several arguments strongly suggest that this network is indeed causing the observed elasticity. Adsorption of F-actin to PC:SA leads more quickly to a slightly more rigid interface with a modulus of mu approximately 50 mN/m. PMID:10049338

75 FR 77574 - Proposed Revision of Class E Airspace; Savoonga, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-13

...-1103Airspace Docket No. 10-AAL-18] Proposed Revision of Class E Airspace; Savoonga, AK AGENCY: Federal Aviation... proposes to revise Class E airspace at Savoonga, AK. The amendment of three Standard Instrument Approach... Operations, Federal Aviation Administration, 222 West 7th Avenue, Box 14, Anchorage, AK 99513-7587. FOR...

76 FR 3011 - Establishment of Class E Airspace; Port Clarence, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-19

...-0354, Airspace Docket No. 10-AAL-10] Establishment of Class E Airspace; Port Clarence, AK AGENCY... Coast Guard Station (CGS) Airport, Port Clarence, AK. The charting of this airspace has been delayed... Administration, 222 West 7th Avenue, Box 14, Anchorage, AK 99513-7587; telephone number (907) 271-5898; fax: (907...

75 FR 81110 - Establishment of Class E Airspace; Port Clarence, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-27

...-0354 Airspace Docket No. 10-AAL-10] Establishment of Class E Airspace; Port Clarence, AK AGENCY...) Airport, Port Clarence, AK, contained in a final rule that was published in the Federal Register. DATES... Aviation Administration, 222 West 7th Avenue, Box 14, Anchorage, AK 99513-7587; telephone number (907) 271...

75 FR 12680 - Revision of Class E Airspace; Scammon Bay, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-17

...-1038; Airspace Docket No. 09-AAL-19] Revision of Class E Airspace; Scammon Bay, AK AGENCY: Federal... Scammon Bay, AK, to accommodate new Area Navigation (RNAV) Standard Instrument Approach Procedures (SIAPs..., 222 West 7th Avenue, Box 14, Anchorage, AK 99513-7587; telephone number (907) 271-5898; fax: (907) 271...

78 FR 17083 - Amendment of Class E Airspace; Scammon Bay, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-20

...-0121; Airspace Docket No. 12-AAL-2] Amendment of Class E Airspace; Scammon Bay, AK AGENCY: Federal... Scammon Bay Airport, Scammon Bay, AK. Controlled airspace is necessary to accommodate aircraft using a new... Federal Register a notice of proposed rulemaking to modify controlled airspace at Scammon Bay, AK (77 FR...

76 FR 21832 - Proposed Revision of Class E Airspace; Yakutat, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-19

...-0244 Airspace Docket No. 11-AAL-05] Proposed Revision of Class E Airspace; Yakutat, AK AGENCY: Federal... proposes to revise Class E airspace at Yakutat, AK. The revision of eight Standard Instrument Approach... Administration, 222 West 7th Avenue, Box 14, Anchorage, AK 99513-7587. FOR FURTHER INFORMATION CONTACT: Martha...

75 FR 30746 - Proposed Revocation and Establishment of Class E Airspace; Northeast, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-02

... Management System Office (see ADDRESSES section for address and phone number) between 9 a.m. and 5 p.m... Distribution System, which describes the application procedure. The Proposal This action proposes to amend.... * * * * * AAL AK E6 Barter Island, AK [Removed] * * * * * AAL AK E6 Mentasta Lake/Mountains Area, AK [Removed...

Mesoscopic model of actin-based propulsion.

PubMed

Zhu, Jie; Mogilner, Alex

2012-01-01

Two theoretical models dominate current understanding of actin-based propulsion: microscopic polymerization ratchet model predicts that growing and writhing actin filaments generate forces and movements, while macroscopic elastic propulsion model suggests that deformation and stress of growing actin gel are responsible for the propulsion. We examine both experimentally and computationally the 2D movement of ellipsoidal beads propelled by actin tails and show that neither of the two models can explain the observed bistability of the orientation of the beads. To explain the data, we develop a 2D hybrid mesoscopic model by reconciling these two models such that individual actin filaments undergoing nucleation, elongation, attachment, detachment and capping are embedded into the boundary of a node-spring viscoelastic network representing the macroscopic actin gel. Stochastic simulations of this 'in silico' actin network show that the combined effects of the macroscopic elastic deformation and microscopic ratchets can explain the observed bistable orientation of the actin-propelled ellipsoidal beads. To test the theory further, we analyze observed distribution of the curvatures of the trajectories and show that the hybrid model's predictions fit the data. Finally, we demonstrate that the model can explain both concave-up and concave-down force-velocity relations for growing actin networks depending on the characteristic time scale and network recoil. To summarize, we propose that both microscopic polymerization ratchets and macroscopic stresses of the deformable actin network are responsible for the force and movement generation.

Polycation induced actin bundles.

PubMed

Muhlrad, Andras; Grintsevich, Elena E; Reisler, Emil

2011-04-01

Three polycations, polylysine, the polyamine spermine and the polycationic protein lysozyme were used to study the formation, structure, ionic strength sensitivity and dissociation of polycation-induced actin bundles. Bundles form fast, simultaneously with the polymerization of MgATP-G-actins, upon the addition of polycations to solutions of actins at low ionic strength conditions. This indicates that nuclei and/or nascent filaments bundle due to attractive, electrostatic effect of polycations and the neutralization of repulsive interactions of negative charges on actin. The attractive forces between the filaments are strong, as shown by the low (in nanomolar range) critical concentration of their bundling at low ionic strength. These bundles are sensitive to ionic strength and disassemble partially in 100 mM NaCl, but both the dissociation and ionic strength sensitivity can be countered by higher polycation concentrations. Cys374 residues of actin monomers residing on neighboring filaments in the bundles can be cross-linked by the short span (5.4Å) MTS-1 (1,1-methanedyl bismethanethiosulfonate) cross-linker, which indicates a tight packing of filaments in the bundles. The interfilament cross-links, which connect monomers located on oppositely oriented filaments, prevent disassembly of bundles at high ionic strength. Cofilin and the polysaccharide polyanion heparin disassemble lysozyme induced actin bundles more effectively than the polylysine-induced bundles. The actin-lysozyme bundles are pathologically significant as both proteins are found in the pulmonary airways of cystic fibrosis patients. Their bundles contribute to the formation of viscous mucus, which is the main cause of breathing difficulties and eventual death in this disorder. Copyright © 2011 Elsevier B.V. All rights reserved.

Nuclear positioning by actin cables and perinuclear actin

PubMed Central

Huelsmann, Sven; Brown, Nicholas H

2014-01-01

Nuclear positioning is an important process during development and homeostasis. Depending on the affected tissue, mislocalized nuclei can alter cellular processes such as polarization, differentiation, or migration and lead ultimately to diseases. Many cells actively control the position of their nucleus using their cytoskeleton and motor proteins. We have recently shown that during Drosophila oogenesis, nurse cells employ cytoplasmic actin cables in association with perinuclear actin to position their nucleus. Here, we briefly summarize our work and discuss why nuclear positioning in nurse cells is specialized but the molecular mechanisms are likely to be more generally used. PMID:24905988

Non-Straub type actin from molluscan catch muscle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shelud'ko, Nikolay S., E-mail: sheludko@stl.ru; Girich, Ulyana V.; Lazarev, Stanislav S.

We have developed a method of obtaining natural actin from smooth muscles of the bivalves on the example of the Crenomytilus grayanus catch muscle. The muscles were previously rigorized to prevent a loss of thin filaments during homogenization and washings. Thin filaments were isolated with a low ionic strength solution in the presence of ATP and sodium pyrophosphate. Surface proteins of thin filaments-tropomyosin, troponin, calponin and some minor actin-binding proteins-were dissociated from actin filaments by increasing the ionic strength to 0.6 M KCL. Natural fibrillar actin obtained in that way depolymerizes easily in low ionic strength solutions commonly used for themore » extraction of Straub-type actin from acetone powder. Purification of natural actin was carried out by the polymerization–depolymerization cycle. The content of inactivated actin remaining in the supernatant is much less than at a similar purification of Straub-type actin. A comparative investigation was performed between the natural mussel actin and the Straub-type rabbit skeletal actin in terms of the key properties of actin: polymerization, activation of Mg-ATPase activity of myosin, and the electron-microscopic structure of actin polymers. -- Highlights: •We developed method of repolymerizable invertebrate smooth muscle actin obtaining. •Our method does not involve use of denaturating agents, which could modify proteins. •Viscosity and polymerization rate of actin, gained that way, is similar to Straub one. •Electron microscopy showed that repolymerized mussel actin is similar to Straub one. •Repolymerized mussel actin has greater ATPase activating capacity, than Straub actin.« less

Photodynamic Therapy for Actinic Keratoses: A Randomized Prospective Non-sponsored Cost-effectiveness Study of Daylight-mediated Treatment Compared with Light-emitting Diode Treatment.

PubMed

Neittaanmäki-Perttu, Noora; Grönroos, Mari; Karppinen, Toni; Snellman, Erna; Rissanen, Pekka

2016-02-01

Daylight-mediated photodynamic therapy (DL-PDT) is considered as effective as conventional PDT using artificial light (light-emitting diode (LED)-PDT) for treatment of actinic keratoses (AK). This randomized prospective non-sponsored study assessed the cost-effectiveness of DL-PDT compared with LED-PDT. Seventy patients with 210 AKs were randomized to DL-PDT or LED-PDT groups. Effectiveness was assessed at 6 months. The costs included societal costs and private costs, including the time patients spent in treatment. Results are presented as incremental cost-effectiveness ratio (ICER). The total costs per patient were significantly lower for DL-PDT (€132) compared with LED-PDT (€170), giving a cost saving of €38 (p = 0.022). The estimated probabilities for patients' complete response were 0.429 for DL-PDT and 0.686 for LED-PDT; a difference in probability of being healed of 0.257. ICER showed a monetary gain of €147 per unit of effectiveness lost. DL-PDT is less costly and less effective than LED-PDT. In terms of cost-effectiveness analysis, DL-PDT provides lower value for money compared with LED-PDT.

The nuclear F-actin interactome of Xenopus oocytes reveals an actin-bundling kinesin that is essential for meiotic cytokinesis

PubMed Central

Samwer, Matthias; Dehne, Heinz-Jürgen; Spira, Felix; Kollmar, Martin; Gerlich, Daniel W; Urlaub, Henning; Görlich, Dirk

2013-01-01

Nuclei of Xenopus laevis oocytes grow 100 000-fold larger in volume than a typical somatic nucleus and require an unusual intranuclear F-actin scaffold for mechanical stability. We now developed a method for mapping F-actin interactomes and identified a comprehensive set of F-actin binders from the oocyte nuclei. Unexpectedly, the most prominent interactor was a novel kinesin termed NabKin (Nuclear and meiotic actin-bundling Kinesin). NabKin not only binds microtubules but also F-actin structures, such as the intranuclear actin bundles in prophase and the contractile actomyosin ring during cytokinesis. The interaction between NabKin and F-actin is negatively regulated by Importin-β and is responsive to spatial information provided by RanGTP. Disconnecting NabKin from F-actin during meiosis caused cytokinesis failure and egg polyploidy. We also found actin-bundling activity in Nabkin's somatic paralogue KIF14, which was previously shown to be essential for somatic cell division. Our data are consistent with the notion that NabKin/KIF14 directly link microtubules with F-actin and that such link is essential for cytokinesis. PMID:23727888

40 CFR Appendixes A-K to Part 51 - [Reserved

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 2 2011-07-01 2011-07-01 false [Reserved] A Appendixes A-K to Part 51 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS REQUIREMENTS FOR PREPARATION, ADOPTION, AND SUBMITTAL OF IMPLEMENTATION PLANS Appendixes A-K to Part 51 [Reserved] ...

40 CFR Appendixes A-K to Part 51 - [Reserved

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 2 2014-07-01 2014-07-01 false [Reserved] A Appendixes A-K to Part 51 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS REQUIREMENTS FOR PREPARATION, ADOPTION, AND SUBMITTAL OF IMPLEMENTATION PLANS Appendixes A-K to Part 51 [Reserved] ...

40 CFR Appendixes A-K to Part 51 - [Reserved

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 2 2013-07-01 2013-07-01 false [Reserved] A Appendixes A-K to Part 51 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS REQUIREMENTS FOR PREPARATION, ADOPTION, AND SUBMITTAL OF IMPLEMENTATION PLANS Appendixes A-K to Part 51 [Reserved] ...

40 CFR Appendixes A-K to Part 51 - [Reserved

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 2 2012-07-01 2012-07-01 false [Reserved] A Appendixes A-K to Part 51 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS REQUIREMENTS FOR PREPARATION, ADOPTION, AND SUBMITTAL OF IMPLEMENTATION PLANS Appendixes A-K to Part 51 [Reserved] ...

40 CFR Appendixes A-K to Part 51 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 2 2010-07-01 2010-07-01 false [Reserved] A Appendixes A-K to Part 51 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS REQUIREMENTS FOR PREPARATION, ADOPTION, AND SUBMITTAL OF IMPLEMENTATION PLANS Appendixes A-K to Part 51 [Reserved] ...

78 FR 65208 - Modification of Class D and E Airspace; Kenai, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

...-1174; Airspace Docket No. 12-AAL-12] Modification of Class D and E Airspace; Kenai, AK AGENCY: Federal... airspace at Kenai Municipal Airport, Kenai, AK. Controlled airspace is necessary to accommodate aircraft... (NPRM) to modify controlled airspace at Kenai Municipal Airport, Kenai, AK (78 FR 34609). Interested...

78 FR 65239 - Proposed Establishment of Class E Airspace; Brevig Mission, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

...-0078; Airspace Docket No. 12-AAL-1] Proposed Establishment of Class E Airspace; Brevig Mission, AK...: This action proposes to establish Class E airspace at Brevig Mission Airport, Brevig Mission, AK... at Brevig Mission Airport, Brevig Mission, AK. Controlled airspace extending 2 miles north, 6 miles...

Immunohistochemical localization of human papilloma virus in conjunctival neoplasias: A retrospective study

PubMed Central

Sharma, Anjana; Panda, Anita

2007-01-01

Background: The extent of association of human papilloma virus (HPV) in human conjunctival neoplasias has been debated in studies originating from different parts of the world, but no substantial evidence has been generated on Indian subjects. This prompted us to carry out a retrospective study on conjunctival neoplasias diagnosed over the past 12 years. Materials and Methods: Histopathological and immunohistochemical analysis of 65 specimens of ocular neoplasias and 30 normal controls diagnosed between 1991 and 2002 at a tertiary eye care hospital, was undertaken. Formalin-fixed, paraffin-embedded tissues were reviewed for confirming histopathological diagnosis, presence of koilocytosis and changes related to actinic keratosis. Immunohistochemical analysis was done using HPV-specific monoclonal antibodies. Clinicopathological correlation and the association of HPV antigen with the histopathological features were performed. Results: Out of the 65 cases analyzed, 35 were papillomas and 30 were ocular surface squamous neoplasias (OSSN). The mean age was 48 years with a male preponderance. Histologically, koilocytosis was observed in 17.1% of papillomas and 36.6% of OSSN. Actinic keratosis was present in 33% of OSSN. Immunohistochemically 17.1% conjunctival papillomas stained positive for HPV antigen, all cases of OSSN were negative for HPV. There was no correlation between koilocytosis or actinic keratosis and the detection of HPV antigen. Conclusions: The association between HPV and conjunctival neoplasias is variable in different geographical areas and also depends on the methods of detection used. This study warrants the need for applying more advanced techniques at a molecular level to determine the possible etiology of HPV in conjunctival neoplasias among Asian-Indians. PMID:17699945

Solar keratosis, pterygium, and squamous cell carcinoma of the conjunctiva in Malawi.

PubMed Central

Clear, A S; Chirambo, M C; Hutt, M S

1979-01-01

The histological features of 234 conjunctival biopsies from Africans in Malawi have been re-examined. The appearances of solar keratosis, pinguecula, and pterygium are presented as part of a continuous spectrum of the same pathological process and aetiology, which may lead to carcinomatous change. The results are discussed with regard to the specific geographical distribution of such lesions found by other workers, with particular emphasis on ultraviolet radiation as the main aetiological factor. Images PMID:427069

Electrostatic interactions between the Bni1p formin FH2 domain and actin influence actin filament nucleation

DOE PAGES

Baker, Joseph L.; Courtemanche, Naomi; Parton, Daniel L.; ...

2014-12-04

Formins catalyze nucleation and growth of actin filaments. In this paper, we study the structure and interactions of actin with the FH2 domain of budding yeast formin Bni1p. We built an all-atom model of the formin dimer on an Oda actin filament 7-mer and studied structural relaxation and interprotein interactions by molecular dynamics simulations. These simulations produced a refined model for the FH2 dimer associated with the barbed end of the filament and showed electrostatic interactions between the formin knob and actin target-binding cleft. Mutations of two formin residues contributing to these interactions (R1423N, K1467L, or both) reduced the interactionmore » energies between the proteins, and in coarse-grained simulations, the formin lost more interprotein contacts with an actin dimer than with an actin 7-mer. Finally, biochemical experiments confirmed a strong influence of these mutations on Bni1p-mediated actin filament nucleation, but not elongation, suggesting that different interactions contribute to these two functions of formins.« less

Doehlert experimental design applied to optimization of light emitting textile structures

NASA Astrophysics Data System (ADS)

Oguz, Yesim; Cochrane, Cedric; Koncar, Vladan; Mordon, Serge R.

2016-07-01

A light emitting fabric (LEF) has been developed for photodynamic therapy (PDT) for the treatment of dermatologic diseases such as Actinic Keratosis (AK). A successful PDT requires homogenous and reproducible light with controlled power and wavelength on the treated skin area. Due to the shape of the human body, traditional PDT with external light sources is unable to deliver homogenous light everywhere on the skin (head vertex, hand, etc.). For better light delivery homogeneity, plastic optical fibers (POFs) have been woven in textile in order to emit laterally the injected light. The previous studies confirmed that the light power could be locally controlled by modifying the radius of POF macro-bendings within the textile structure. The objective of this study is to optimize the distribution of macro-bendings over the LEF surface in order to increase the light intensity (mW/cm2), and to guarantee the best possible light deliver homogeneity over the LEF which are often contradictory. Fifteen experiments have been carried out with Doehlert experimental design involving Response Surface Methodology (RSM). The proposed models are fitted to the experimental data to enable the optimal set up of the warp yarns tensions.

78 FR 48299 - Establishment of Class D Airspace; Bryant AAF, Anchorage, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-08

...-0433; Airspace Docket No. 12-AAL-5] Establishment of Class D Airspace; Bryant AAF, Anchorage, AK AGENCY... airspace at Bryant Army Airfield (AAF), Anchorage AK. This action provides controlled airspace to improve... proposed rulemaking (NPRM) to establish Class D airspace at Bryant AAF, Anchorage AK (77 FR 50646...

78 FR 30797 - Proposed Amendment of Class E Airspace; Point Thomson, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-23

...-1175; Airspace Docket No. 12-AAL-11] Proposed Amendment of Class E Airspace; Point Thomson, AK AGENCY... action proposes to modify the airspace at Point Thomson, AK by establishing Class E Airspace at Point Thomson Airstrip Airport, Point Thomson, AK. This will accommodate aircraft using a new Area Navigation...

Plasma levels of F-actin and F:G-actin ratio as potential new biomarkers in patients with septic shock.

PubMed

Belsky, Justin B; Morris, Daniel C; Bouchebl, Ralph; Filbin, Michael R; Bobbitt, Kevin R; Jaehne, Anja K; Rivers, Emanuel P

2016-01-01

To compare plasma levels of F-actin, G-actin and thymosin beta 4 (TB4) in humans with septic shock, noninfectious systemic inflammatory response syndrome (SIRS) and healthy controls. F-actin was significantly elevated in septic shock as compared with noninfectious SIRS and healthy controls. G-actin levels were greatest in the noninfectious SIRS group but significantly elevated in septic shock as compared with healthy controls. TB4 was not detectable in the septic shock or noninfectious SIRS group above the assay's lowest detection range (78 ng/ml). F-actin is significantly elevated in patients with septic shock as compared with noninfectious SIRS. F-actin and the F:G-actin ratio are potential biomarkers for the diagnosis of septic shock.

A systems-biology approach to yeast actin cables.

PubMed

Drake, Tyler; Yusuf, Eddy; Vavylonis, Dimitrios

2012-01-01

We focus on actin cables in yeast as a model system for understanding cytoskeletal organization and the workings of actin itself. In particular, we highlight quantitative approaches on the kinetics of actin-cable assembly and methods of measuring their morphology by image analysis. Actin cables described by these studies can span greater lengths than a thousand end-to-end actin-monomers. Because of this difference in length scales, control of the actin-cable system constitutes a junction between short-range interactions - among actin-monomers and nucleating, polymerization-facilitating, side-binding, severing, and cross-linking proteins - and the emergence of cell-scale physical form as embodied by the actin cables themselves.

Stochastic Severing of Actin Filaments by Actin Depolymerizing Factor/Cofilin Controls the Emergence of a Steady Dynamical Regime

PubMed Central

Roland, Jeremy; Berro, Julien; Michelot, Alphée; Blanchoin, Laurent; Martiel, Jean-Louis

2008-01-01

Actin dynamics (i.e., polymerization/depolymerization) powers a large number of cellular processes. However, a great deal remains to be learned to explain the rapid actin filament turnover observed in vivo. Here, we developed a minimal kinetic model that describes key details of actin filament dynamics in the presence of actin depolymerizing factor (ADF)/cofilin. We limited the molecular mechanism to 1), the spontaneous growth of filaments by polymerization of actin monomers, 2), the ageing of actin subunits in filaments, 3), the cooperative binding of ADF/cofilin to actin filament subunits, and 4), filament severing by ADF/cofilin. First, from numerical simulations and mathematical analysis, we found that the average filament length, 〈L〉, is controlled by the concentration of actin monomers (power law: 5/6) and ADF/cofilin (power law: −2/3). We also showed that the average subunit residence time inside the filament, 〈T〉, depends on the actin monomer (power law: −1/6) and ADF/cofilin (power law: −2/3) concentrations. In addition, filament length fluctuations are ∼20% of the average filament length. Moreover, ADF/cofilin fragmentation while modulating filament length keeps filaments in a high molar ratio of ATP- or ADP-Pi versus ADP-bound subunits. This latter property has a protective effect against a too high severing activity of ADF/cofilin. We propose that the activity of ADF/cofilin in vivo is under the control of an affinity gradient that builds up dynamically along growing actin filaments. Our analysis shows that ADF/cofilin regulation maintains actin filaments in a highly dynamical state compatible with the cytoskeleton dynamics observed in vivo. PMID:18065447

Geometrical and Mechanical Properties Control Actin Filament Organization

PubMed Central

Ennomani, Hajer; Théry, Manuel; Nedelec, Francois; Blanchoin, Laurent

2015-01-01

The different actin structures governing eukaryotic cell shape and movement are not only determined by the properties of the actin filaments and associated proteins, but also by geometrical constraints. We recently demonstrated that limiting nucleation to specific regions was sufficient to obtain actin networks with different organization. To further investigate how spatially constrained actin nucleation determines the emergent actin organization, we performed detailed simulations of the actin filament system using Cytosim. We first calibrated the steric interaction between filaments, by matching, in simulations and experiments, the bundled actin organization observed with a rectangular bar of nucleating factor. We then studied the overall organization of actin filaments generated by more complex pattern geometries used experimentally. We found that the fraction of parallel versus antiparallel bundles is determined by the mechanical properties of actin filament or bundles and the efficiency of nucleation. Thus nucleation geometry, actin filaments local interactions, bundle rigidity, and nucleation efficiency are the key parameters controlling the emergent actin architecture. We finally simulated more complex nucleation patterns and performed the corresponding experiments to confirm the predictive capabilities of the model. PMID:26016478

Boolean gates on actin filaments

NASA Astrophysics Data System (ADS)

Siccardi, Stefano; Tuszynski, Jack A.; Adamatzky, Andrew

2016-01-01

Actin is a globular protein which forms long polar filaments in the eukaryotic cytoskeleton. Actin networks play a key role in cell mechanics and cell motility. They have also been implicated in information transmission and processing, memory and learning in neuronal cells. The actin filaments have been shown to support propagation of voltage pulses. Here we apply a coupled nonlinear transmission line model of actin filaments to study interactions between voltage pulses. To represent digital information we assign a logical TRUTH value to the presence of a voltage pulse in a given location of the actin filament, and FALSE to the pulse's absence, so that information flows along the filament with pulse transmission. When two pulses, representing Boolean values of input variables, interact, then they can facilitate or inhibit further propagation of each other. We explore this phenomenon to construct Boolean logical gates and a one-bit half-adder with interacting voltage pulses. We discuss implications of these findings on cellular process and technological applications.

Actin filaments-A target for redox regulation.

PubMed

Wilson, Carlos; Terman, Jonathan R; González-Billault, Christian; Ahmed, Giasuddin

2016-10-01

Actin and its ability to polymerize into dynamic filaments is critical for the form and function of cells throughout the body. While multiple proteins have been characterized as affecting actin dynamics through noncovalent means, actin and its protein regulators are also susceptible to covalent modifications of their amino acid residues. In this regard, oxidation-reduction (Redox) intermediates have emerged as key modulators of the actin cytoskeleton with multiple different effects on cellular form and function. Here, we review work implicating Redox intermediates in post-translationally altering actin and discuss what is known regarding how these alterations affect the properties of actin. We also focus on two of the best characterized enzymatic sources of these Redox intermediates-the NADPH oxidase NOX and the flavoprotein monooxygenase MICAL-and detail how they have both been identified as altering actin, but share little similarity and employ different means to regulate actin dynamics. Finally, we discuss the role of these enzymes and redox signaling in regulating the actin cytoskeleton in vivo and highlight their importance for neuronal form and function in health and disease. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Actin dynamics in Amoeba proteus motility.

PubMed

Pomorski, P; Krzemiński, P; Wasik, A; Wierzbicka, K; Barańska, J; Kłopocka, W

2007-01-01

We studied the distribution of the endogenous Arp2/3 complex in Amoeba proteus and visualised the ratio of filamentous (F-actin) to total actin in living cells. The presented results show that in the highly motile Amoeba proteus, Arp2/3 complex-dependent actin polymerisation is involved in the formation of the branching network of the contractile layer, adhesive structures, and perinuclear cytoskeleton. The aggregation of the Arp2/3 complex in the cortical network, with the exception of the uroid and advancing fronts, and the spatial orientation of microfilaments at the leading edge suggest that actin polymerisation in this area is not sufficient to provide the driving force for membrane displacement. The examined proteins were enriched in the pinocytotic pseudopodia and the perinuclear cytoskeleton in pinocytotic amoebae. In migrating amoebae, the course of changes in F-actin concentration corresponded with the distribution of tension in the cell cortex. The maximum level of F-actin in migrating amoebae was observed in the middle-posterior region and in the front of retracting pseudopodia. Arp2/3 complex-dependent actin polymerisation did not seem to influence F-actin concentration. The strongly condensed state of the microfilament system could be attributed to strong isometric contraction of the cortical layer accompanied by its retraction from distal cell regions. Isotonic contraction was limited to the uroid.

Autofluorescence of seborrheic keratosis (warts) and of tissue surrounding malignant tumors

NASA Astrophysics Data System (ADS)

Lohmann, Wolfgang; Schill, Wolf-Bernhard; Bohle, Rainer M.; Dreyer, Thomas

1997-12-01

Autofluorescence measurements on human tissue have revealed a decrease in intensity in malignant tumors and an increase in the healthy region adjacent to the tumor. This latter event might serve as a protective wall against the invasive tumor cells. The composition of this wall is still unknown. Antioxidants such as NADH might be involved. In the case of seborrheic keratosis (wart), the intensity is increased in the pigmented spots. Care must be taken, therefore, when warts are attached to malignant tumors. The resulting value is, then, not indicative for the condition of the system.

The role of immunosuppression in squamous cell carcinomas arising in seborrheic keratosis.

PubMed

Conic, Ruzica Z; Napekoski, Karl; Schuetz, Heidi; Piliang, Melissa; Bergfeld, Wilma; Atanaskova Mesinkovska, Natasha

2017-06-01

Seborrheic keratoses (SK) are common skin neoplasms considered to be benign. Reports of associated squamous cell carcinoma arising within seborrheic keratosis (SCC-SK) have been described. To describe the histopathologic characteristics of SCC-SK and identify predisposing factors in formation of these rare lesions. There were 162 cases of SCC-SK in a span of a decade (2003-2014). All of the histopathologic specimens and medical records were reviewed. Data from these patients were compared to a control group with seborrheic keratosis who were matched by age, sex, and location of lesion from the same time period (n = 162). SCC-SK has the classic histopathologic features of SK, such as hyperkeratosis, parakeratosis, papillomatosis, and pseudohorn cysts. The areas of squamous cell carcinoma were characterized by areas of squamous dysplasia (100%), hypogranulosis (79.6%), squamous eddies (79.6%), solar elastosis (80.9%), and brown pigmentation (59.9%). Patients with a history of immunosuppression had an increased risk for developing SCC-SK (19% vs 3%; P < .01), particularly when inhibition was transplant-associated (10% vs 0%; P < .01). This was a single center, retrospective study. SCC-SK occurs more often in elderly men with a history of immunosuppression associated with organ transplants. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

A Systems-Biology Approach to Yeast Actin Cables

PubMed Central

Drake, Tyler; Yusuf, Eddy; Vavylonis, Dimitrios

2011-01-01

We focus on actin cables in yeast as a model system for understanding cytoskeletal organization and the workings of actin itself. In particular, we highlight quantitative approaches on the kinetics of actin cable assembly and methods of measuring their morphology by image analysis. Actin cables described by these studies can span greater lengths than a thousand end-to-end actin monomers. Because of this difference in length scales, control of the actin-cable system constitutes a junction between short-range interactions—among actin monomers and nucleating, polymerization-facilitating, side-binding, severing, and cross-linking proteins—and the emergence of cell-scale physical form as embodied by the actin cables themselves. PMID:22161338

Allele-specific Effects of Human Deafness γ-Actin Mutations (DFNA20/26) on the Actin/Cofilin Interaction*

PubMed Central

Bryan, Keith E.; Rubenstein, Peter A.

2009-01-01

Auditory hair cell function requires proper assembly and regulation of the nonmuscle gamma isoactin-rich cytoskeleton, and six point mutations in this isoactin cause a type of delayed onset autosomal dominant nonsyndromic progressive hearing loss, DFNA20/26. The molecular basis underlying this actin-dependent hearing loss is unknown. To address this problem, the mutations have been introduced into yeast actin, and their effects on actin function were assessed in vivo and in vitro. Because we previously showed that polymerization was unaffected in five of the six mutants, we have focused on proteins that regulate actin, in particular cofilin, which severs F-actin and sequesters actin monomers. The mutations do not affect the interaction of cofilin with G-actin. However, T89I and V370A mutant F-actins are much more susceptible to cofilin disassembly than WT filaments in vitro. Conversely, P332A filaments demonstrate enhanced resistance. Wild type actin solutions containing T89I, K118M, or P332A mutant actins at mole fractions similar to those found in the hair cell respond in vitro toward cofilin in a manner proportional to the level of the mutant present. Finally, depression of cofilin action in vivo by elimination of the cofilin-activating protein, Aip1p, rescues the inability to grow on glycerol caused by K118M, T278I, P332A, and V370A. These results suggest that a filament instability caused by these mutations can be balanced by decreasing a system in vivo that promotes increased filament turnover. Such mutant-dependent filament destabilization could easily result in hair cell malfunction leading to the late-onset hearing loss observed in these patients. PMID:19419963

EIF2AK4 Mutations in Patients Diagnosed With Pulmonary Arterial Hypertension.

PubMed

Best, D Hunter; Sumner, Kelli L; Smith, Benjamin P; Damjanovich-Colmenares, Kristy; Nakayama, Ikue; Brown, Lynette M; Ha, Youna; Paul, Eleri; Morris, Ashley; Jama, Mohamed A; Dodson, Mark W; Bayrak-Toydemir, Pinar; Elliott, C Gregory

2017-04-01

Differentiating pulmonary venoocclusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) from idiopathic pulmonary arterial hypertension (IPAH) or heritable pulmonary arterial hypertension (HPAH) is important clinically. Mutations in eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) cause heritable PVOD and PCH, whereas mutations in other genes cause HPAH. The aim of this study was to describe the frequency of pathogenic EIF2AK4 mutations in patients diagnosed clinically with IPAH or HPAH. Sanger sequencing and deletion/duplication analysis were performed to detect mutations in the bone morphogenetic protein receptor type II (BMPR2) gene in 81 patients diagnosed at 30 North American medical centers with IPAH (n = 72) or HPAH (n = 9). BMPR2 mutation-negative patients (n = 67) were sequenced for mutations in four other genes (ACVRL1, ENG, CAV1, and KCNK3) known to cause HPAH. Patients negative for mutations in all known PAH genes (n = 66) were then sequenced for mutations in EIF2AK4. We assessed the pathogenicity of EIF2AK4 mutations and reviewed clinical characteristics of patients with pathogenic EIF2AK4 mutations. Pathogenic BMPR2 mutations were identified in 8 of 72 (11.1%) patients with IPAH and 6 of 9 (66.7%) patients with HPAH. A novel homozygous EIF2AK4 mutation (c.257+4A>C) was identified in 1 of 9 (11.1%) patients diagnosed with HPAH. The novel EIF2AK4 mutation (c.257+4A>C) was homozygous in two sisters with severe pulmonary hypertension. None of the 72 patients with IPAH had biallelic EIF2AK4 mutations. Pathogenic biallelic EIF2AK4 mutations are rarely identified in patients diagnosed with HPAH. Identification of pathogenic biallelic EIF2AK4 mutations can aid clinicians in differentiating HPAH from heritable PVOD or PCH. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

75 FR 26151 - Proposed Revision of Class E Airspace; Kulik Lake, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-11

...-0270 Airspace Docket No. 10-AAL-8] Proposed Revision of Class E Airspace; Kulik Lake, AK AGENCY... action proposes to revise Class E airspace at Kulik Lake, AK. This action would correct an error in the... Administration, 222 West 7th Avenue, Box 14, Anchorage, AK 99513-7587. FOR FURTHER INFORMATION CONTACT: Gary Rolf...

F-Actin Dynamics in Neurospora crassa ▿ †

PubMed Central

Berepiki, Adokiye; Lichius, Alexander; Shoji, Jun-Ya; Tilsner, Jens; Read, Nick D.

2010-01-01

This study demonstrates the utility of Lifeact for the investigation of actin dynamics in Neurospora crassa and also represents the first report of simultaneous live-cell imaging of the actin and microtubule cytoskeletons in filamentous fungi. Lifeact is a 17-amino-acid peptide derived from the nonessential Saccharomyces cerevisiae actin-binding protein Abp140p. Fused to green fluorescent protein (GFP) or red fluorescent protein (TagRFP), Lifeact allowed live-cell imaging of actin patches, cables, and rings in N. crassa without interfering with cellular functions. Actin cables and patches localized to sites of active growth during the establishment and maintenance of cell polarity in germ tubes and conidial anastomosis tubes (CATs). Recurrent phases of formation and retrograde movement of complex arrays of actin cables were observed at growing tips of germ tubes and CATs. Two populations of actin patches exhibiting slow and fast movement were distinguished, and rapid (1.2 μm/s) saltatory transport of patches along cables was observed. Actin cables accumulated and subsequently condensed into actin rings associated with septum formation. F-actin organization was markedly different in the tip regions of mature hyphae and in germ tubes. Only mature hyphae displayed a subapical collar of actin patches and a concentration of F-actin within the core of the Spitzenkörper. Coexpression of Lifeact-TagRFP and β-tubulin–GFP revealed distinct but interrelated localization patterns of F-actin and microtubules during the initiation and maintenance of tip growth. PMID:20139238

Follicular keratosis of the chin treated with 1.24R-dihydroxyvitamin D3 ointment.

PubMed

Yanagihara, Makoto; Takeda, Kiminobu; Tanabe, Hiroshi; Abe, Shinya; Ishizaki, Hiroshi

2007-01-01

In follicular keratosis of the chin, keratotic follicular papules occur on the chin and jaw due to localized prolonged pressure and friction on the naked skin. We present one patient with this disorder. The dermatoscopic examination revealed many well-demarcated yellow spindle bodies in the patchy lesion. Therapy with 1.24R-dihydroxyvitamin D3 ointment was effective during the treatment but had no residual positive effect.

Actinic comedonal plaque.

PubMed

Eastern, J S; Martin, S

1980-12-01

Solitary plaques developed on the sun-exposed and damaged skin of five elderly, fair-skinned individuals. The lesions, erythematous to bluish confluent nodules and plaques with a cribriform appearance and comedone-like structures, presented a distinctive histologic picture of dilated, keratin-filled follicles within a matrix of amorphous, damaged collagen. We believe these cases demonstrate a distinct entity within the realm of actinic dermatoses, for which the name "actinic comedonal plaque" seems appropriate.

Control of the actin cytoskeleton in root hair development.

PubMed

Pei, Weike; Du, Fei; Zhang, Yi; He, Tian; Ren, Haiyun

2012-05-01

The development of root hair includes four stages: bulge site selection, bulge formation, tip growth, and maturation. The actin cytoskeleton is involved in all of these stages and is organized into distinct arrangements in the different stages. In addition to the actin configuration, actin isoforms also play distinct roles in the different stages. The actin cytoskeleton is regulated by actin-binding proteins, such as formin, Arp2/3 complex, profilin, actin depolymerizing factor, and villin. Some upstream signals, i.e. calcium, phospholipids, and small GTPase regulate the activity of these actin-binding proteins to produce the proper actin configuration. We constructed a working model on how the actin cytoskeleton is controlled by actin-binding proteins and upstream signaling in root hair development based on the current literature: at the tip of hairs, actin polymerization appears to be facilitated by Arp2/3 complex that is activated by small GTPase, and profilin that is regulated by phosphatidylinositol 4,5-bisphosphate. Meanwhile, actin depolymerization and turnover are likely mediated by villin and actin depolymerizing factor, which are stimulated by calcium. At the shank, actin cables are produced by formin and villin. Under the complicated interaction, the actin cytoskeleton is controlled spatially and temporally during root hair development. © 2012 Elsevier Ireland Ltd. All rights reserved.

Dermoscopy-pathology relationship in seborrheic keratosis.

PubMed

Minagawa, Akane

2017-05-01

Making a definitive diagnosis of seborrheic keratosis (SK) can be challenging for the naked eye due to its wide variation in clinical features. Fortunately, however, most cases of SK exhibit the typical dermoscopic findings of fissures and ridges, hairpin vessels with white halo, comedo-like openings, and milia-like cysts, all of which are helpful to distinguish SK from melanoma, melanocytic nevus, squamous cell carcinoma, basal cell carcinoma (BCC) and other skin tumors. Histopathologically, these dermoscopic characteristics correspond to papillomatous surface of the epidermis, enlarged capillaries of the dermal papillae, pseudohorn cysts in the epidermis opened to the surface of the lesion and intraepidermal cysts, respectively. Clinicians should bear in mind that the clonal type of SK dermoscopically mimics melanoma and BCC by the presence of globule-like structures, while regressing SK exhibits a granular pattern that is similar to the peppering found in melanoma. Furthermore, milia-like cysts alone are insufficient for a conclusive diagnosis of SK because melanoma in rare cases displays cysts along with other SK-like dermoscopic findings. © 2017 Japanese Dermatological Association.

Disrupting actin-myosin-actin connectivity in airway smooth muscle as a treatment for asthma?

PubMed

Lavoie, Tera L; Dowell, Maria L; Lakser, Oren J; Gerthoffer, William T; Fredberg, Jeffrey J; Seow, Chun Y; Mitchell, Richard W; Solway, Julian

2009-05-01

Breathing is known to functionally antagonize bronchoconstriction caused by airway muscle contraction. During breathing, tidal lung inflation generates force fluctuations that are transmitted to the contracted airway muscle. In vitro, experimental application of force fluctuations to contracted airway smooth muscle strips causes them to relengthen. Such force fluctuation-induced relengthening (FFIR) likely represents the mechanism by which breathing antagonizes bronchoconstriction. Thus, understanding the mechanisms that regulate FFIR of contracted airway muscle could suggest novel therapeutic interventions to increase FFIR, and so to enhance the beneficial effects of breathing in suppressing bronchoconstriction. Here we propose that the connectivity between actin filaments in contracting airway myocytes is a key determinant of FFIR, and suggest that disrupting actin-myosin-actin connectivity by interfering with actin polymerization or with myosin polymerization merits further evaluation as a potential novel approach for preventing prolonged bronchoconstriction in asthma.

Structure of the Rigor Actin-Tropomyosin-Myosin Complex

PubMed Central

Behrmann, Elmar; Müller, Mirco; Penczek, Pawel A.; Mannherz, Hans Georg; Manstein, Dietmar J.; Raunser, Stefan

2014-01-01

The interaction of myosin with actin filaments is the central feature of muscle contraction and cargo movement along actin filaments of the cytoskeleton. Myosin converts the chemical energy stored in ATP into force and movement along actin filaments. Myosin binding to actin induces conformational changes that are coupled to the nucleotide-binding pocket and amplified by a specialized region of the motor domain for efficient force generation. Tropomyosin plays a key role in regulating the productive interaction between myosins and actin. Here, we report the 8 Å resolution structure of the actin-tropomyosin-myosin complex determined by cryo electron microscopy. The pseudo-atomic model of the complex obtained from fitting crystal structures into the map defines the large actin-myosin-tropomyosin interface and the molecular interactions between the proteins in detail and allows us to propose a structural model for tropomyosin dependent myosin binding to actin and actin-induced nucleotide release from myosin. PMID:22817895

Daylight-mediated photodynamic therapy in Spain: advantages and disadvantages.

PubMed

Pérez-Pérez, L; García-Gavín, J; Gilaberte, Y

2014-09-01

Photodynamic therapy (PDT) is an option for the treatment of actinic keratosis, Bowen disease, and certain types of basal cell carcinoma. It is also used to treat various other types of skin condition, including inflammatory and infectious disorders. The main disadvantages of PDT are the time it takes to administer (both for the patient and for health professionals) and the pain associated with treatment. Daylight-mediated PDT has recently been reported to be an alternative to the conventional approach. Several studies have shown it to be similar in efficacy to and better tolerated than classic PDT for the treatment of mild to moderate actinic keratosis. Nevertheless, most of these studies are from northern Europe, and no data have been reported from southern Europe. The present article reviews the main studies published to date, presents the treatment protocol, and summarizes our experience with a group of treated patients. Copyright © 2013 Elsevier España, S.L.U. y AEDV. All rights reserved.

Actin Age Orchestrates Myosin-5 and Myosin-6 Runlengths

PubMed Central

Zimmermann, Dennis; Santos, Alicja; Kovar, David R.; Rock, Ronald S.

2015-01-01

Summary Unlike a static and immobile skeleton, the actin cytoskeleton is a highly dynamic network of filamentous actin (F-actin) polymers that continuously turn over. In addition to generating mechanical forces and sensing mechanical deformation, dynamic F-actin networks serve as cellular tracks for myosin motor traffic. However, much of our mechanistic understanding of processive myosins comes from in vitro studies where motility was studied on pre-assembled and artificially stabilized, static F-actin tracks. In this work, we examine the role of actin dynamics in single-molecule myosin motility using assembling F-actin and the two highly processive motors, myosin-5 and myosin-6. These two myosins have distinct functions in the cell and travel in opposite directions along actin filaments [1–3]. Myosin-5 walks towards the barbed ends of F-actin, traveling to sites of actin polymerization at the cell periphery [4]. Myosin-6 walks towards the pointed end of F-actin [5], traveling towards the cell center along older segments of the actin filament. We find that myosin-5 takes 1.3 to 1.5-fold longer runs on ADP•Pi (young) F-actin, while myosin-6 takes 1.7 to 3.6-fold longer runs along ADP (old) F-actin. These results suggest that conformational differences between ADP•Pi and ADP F-actin tailor these myosins to walk farther toward their preferred actin filament end. Taken together, these experiments define a new mechanism by which myosin traffic may sort to different F-actin networks depending on filament age. PMID:26190073

Actin expression in some Platyhelminthe species.

PubMed

Fagotti, A; Panara, F; Di Rosa, I; Simoncelli, F; Gabbiani, G; Pascolini, R

1994-10-01

Actin expression in some Platyhelminthe species was demonstrated by western-blotting and immunocytochemical analysis using two distinct anti-actin antibodies: the anti-total actin that reacts against all actin isoforms of higher vertebrates and the anti-alpha SM-1 that recognizes the alpha-smooth muscle (alpha SM) isotype of endothermic vertebrates (Skalli et al., 1986). Western-blotting experiments showed that all species tested, including some free-living Platyhelminthes (Tricladida and Rhabdocoela) and the parasitic Fasciola hepatica, were stained by anti-total actin antibody while only Dugesidae and Dendrocoelidae showed a positive immunoreactivity against anti-alpha SM-1. These results were confirmed by cytochemical immunolocalization using both avidin biotin conjugated peroxidase reaction on paraffin sections, and immunogold staining on Lowicryl 4KM embedded specimens. Our findings may contribute to the understanding of Platyhelminthes phylogeny.

EIF2AK4 Mutations in Pulmonary Capillary Hemangiomatosis

PubMed Central

Best, D. Hunter; Sumner, Kelli L.; Austin, Eric D.; Chung, Wendy K.; Brown, Lynette M.; Borczuk, Alain C.; Rosenzweig, Erika B.; Bayrak-Toydemir, Pinar; Mao, Rong; Cahill, Barbara C.; Tazelaar, Henry D.; Leslie, Kevin O.; Hemnes, Anna R.; Robbins, Ivan M.

2014-01-01

Background: Pulmonary capillary hemangiomatosis (PCH) is a rare disease of capillary proliferation of unknown cause and with a high mortality. Families with multiple affected individuals with PCH suggest a heritable cause although the genetic etiology remains unknown. Methods: We used exome sequencing to identify a candidate gene for PCH in a family with two affected brothers. We then screened 11 unrelated patients with familial (n = 1) or sporadic (n = 10) PCH for mutations. Results: Using exome sequencing, we identified compound mutations in eukaryotic translation initiation factor 2 α kinase 4 (EIF2AK4) (formerly known as GCN2) in both affected brothers. Both parents and an unaffected sister were heterozygous carriers. In addition, we identified two EIF2AK4 mutations in each of two of 10 unrelated individuals with sporadic PCH. EIF2AK4 belongs to a family of kinases that regulate angiogenesis in response to cellular stress. Conclusions: Mutations in EIF2AK4 are likely to cause autosomal-recessive PCH in familial and some nonfamilial cases. PMID:24135949

Bulkiness or aromatic nature of tyrosine-143 of actin is important for the weak binding between F-actin and myosin-ADP-phosphate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gomibuchi, Yuki; Uyeda, Taro Q.P.; Wakabayashi, Takeyuki, E-mail: tw007@nasu.bio.teikyo-u.ac.jp

2013-11-29

Highlights: •The effect of mutation of Tyr143 that becomes more exposed on assembly was examined. •Mutation of tyrosine-143 of Dictyostelium actin changed actin polymerizability. •The bulkiness or aromatic nature of Tyr143 is important for the weak binding. •The weak interaction between myosin and actin strengthened by Tyr143Trp mutation. -- Abstract: Actin filaments (F-actin) interact with myosin and activate its ATPase to support force generation. By comparing crystal structures of G-actin and the quasi-atomic model of F-actin based on high-resolution cryo-electron microscopy, the tyrosine-143 was found to be exposed more than 60 Å{sup 2} to the solvent in F-actin. Because tyrosine-143more » flanks the hydrophobic cleft near the hydrophobic helix that binds to myosin, the mutant actins, of which the tyrosine-143 was replaced with tryptophan, phenylalanine, or isoleucine, were generated using the Dictyostelium expression system. It polymerized significantly poorly when induced by NaCl, but almost normally by KCl. In the presence of phalloidin and KCl, the extents of the polymerization of all the mutant actins were comparable to that of the wild-type actin so that the actin-activated myosin ATPase activity could be reliably compared. The affinity of skeletal heavy meromyosin to F-actin and the maximum ATPase activity (V{sub max}) were estimated by a double reciprocal plot. The Tyr143Trp-actin showed the higher affinity (smaller K{sub app}) than that of the wild-type actin, with the V{sub max} being almost unchanged. The K{sub app} and V{sub max} of the Tyr143Phe-actin were similar to those of the wild-type actin. However, the activation by Tyr143Ile-actin was much smaller than the wild-type actin and the accurate determination of K{sub app} was difficult. Comparison of the myosin ATPase activated by the various mutant actins at the same concentration of F-actin showed that the extent of activation correlates well with the solvent-accessible surface areas

Actin growth profile in clathrin-mediated endocytosis

NASA Astrophysics Data System (ADS)

Tweten, D. J.; Bayly, P. V.; Carlsson, A. E.

2017-05-01

Clathrin-mediated endocytosis in yeast is driven by a protein patch containing close to 100 different types of proteins. Among the proteins are 5000 -10 000 copies of polymerized actin, and successful endocytosis requires growth of the actin network. Since it is not known exactly how actin network growth drives endocytosis, we calculate the spatial distribution of actin growth required to generate the force that drives the process. First, we establish the force distribution that must be supplied by actin growth, by combining membrane-bending profiles obtained via electron microscopy with established theories of membrane mechanics. Next, we determine the profile of actin growth, using a continuum mechanics approach and an iterative procedure starting with an actin growth profile obtained from a linear analysis. The profile has fairly constant growth outside a central hole of radius 45-50 nm, but very little growth in this hole. This growth profile can reproduce the required forces if the actin shear modulus exceeds 80 kPa, and the growing filaments can exert very large polymerization forces. The growth profile prediction could be tested via electron-microscopy or super-resolution experiments in which the turgor pressure is suddenly turned off.

Interactions of histatin-3 and histatin-5 with actin.

PubMed

Blotnick, Edna; Sol, Asaf; Bachrach, Gilad; Muhlrad, Andras

2017-03-06

Histatins are histidine rich polypeptides produced in the parotid and submandibular gland and secreted into the saliva. Histatin-3 and -5 are the most important polycationic histatins. They possess antimicrobial activity against fungi such as Candida albicans. Histatin-5 has a higher antifungal activity than histatin-3 while histatin-3 is mostly involved in wound healing in the oral cavity. We found that these histatins, like other polycationic peptides and proteins, such as LL-37, lysozyme and histones, interact with extracellular actin. Histatin-3 and -5 polymerize globular actin (G-actin) to filamentous actin (F-actin) and bundle F-actin filaments. Both actin polymerization and bundling by histatins is pH sensitive due to the high histidine content of histatins. In spite of the equal number of net positive charges and histidine residues in histatin-3 and -5, less histatin-3 is needed than histatin-5 for polymerization and bundling of actin. The efficiency of actin polymerization and bundling by histatins greatly increases with decreasing pH. Histatin-3 and -5 induced actin bundles are dissociated by 100 and 50 mM NaCl, respectively. The relatively low NaCl concentration required to dissociate histatin-induced bundles implies that the actin-histatin filaments bind to each other mainly by electrostatic forces. The binding of histatin-3 to F-actin is stronger than that of histatin-5 showing that hydrophobic forces have also some role in histatin-3- actin interaction. Histatins affect the fluorescence of probes attached to the D-loop of G-actin indicating histatin induced changes in actin structure. Transglutaminase cross-links histatins to actin. Competition and limited proteolysis experiments indicate that the main histatin cross-linking site on actin is glutamine-49 on the D-loop of actin. Both histatin-3 and -5 interacts with actin, however, histatin 3 binds stronger to actin and affects actin structure at lower concentration than histatin-5 due to the extra 8

A dynamic formin-dependent deep F-actin network in axons

PubMed Central

Ganguly, Archan; Tang, Yong; Wang, Lina; Ladt, Kelsey; Loi, Jonathan; Dargent, Bénédicte; Leterrier, Christophe

2015-01-01

Although actin at neuronal growth cones is well-studied, much less is known about actin organization and dynamics along axon shafts and presynaptic boutons. Using probes that selectively label filamentous-actin (F-actin), we found focal “actin hotspots” along axons—spaced ∼3–4 µm apart—where actin undergoes continuous assembly/disassembly. These foci are a nidus for vigorous actin polymerization, generating long filaments spurting bidirectionally along axons—a phenomenon we call “actin trails.” Super-resolution microscopy reveals intra-axonal deep actin filaments in addition to the subplasmalemmal “actin rings” described recently. F-actin hotspots colocalize with stationary axonal endosomes, and blocking vesicle transport diminishes the actin trails, suggesting mechanistic links between vesicles and F-actin kinetics. Actin trails are formin—but not Arp2/3—dependent and help enrich actin at presynaptic boutons. Finally, formin inhibition dramatically disrupts synaptic recycling. Collectively, available data suggest a two-tier F-actin organization in axons, with stable “actin rings” providing mechanical support to the plasma membrane and dynamic "actin trails" generating a flexible cytoskeletal network with putative physiological roles. PMID:26216902

Three’s company: The fission yeast actin cytoskeleton

PubMed Central

Kovar, David R.; Sirotkin, Vladimir; Lord, Matthew

2010-01-01

How the actin cytoskeleton assembles into different structures to drive diverse cellular processes is a fundamental cell biological question. In addition to orchestrating the appropriate combination of regulators and actin-binding proteins, different actin-based structures must insulate themselves from one another to maintain specificity within a crowded cytoplasm. Actin specification is particularly vexing in complex eukaryotes where a multitude of protein isoforms and actin structures operate within the same cell. Fission yeast Schizosaccharomyces pombe possesses a single actin isoform that functions in three distinct structures throughout the cell cycle. In this review, we explore recent studies in fission yeast that help unravel how different actin structures operate in cells. PMID:21145239

The nature of the globular- to fibrous-actin transition.

PubMed

Oda, Toshiro; Iwasa, Mitsusada; Aihara, Tomoki; Maéda, Yuichiro; Narita, Akihiro

2009-01-22

Actin plays crucial parts in cell motility through a dynamic process driven by polymerization and depolymerization, that is, the globular (G) to fibrous (F) actin transition. Although our knowledge about the actin-based cellular functions and the molecules that regulate the G- to F-actin transition is growing, the structural aspects of the transition remain enigmatic. We created a model of F-actin using X-ray fibre diffraction intensities obtained from well oriented sols of rabbit skeletal muscle F-actin to 3.3 A in the radial direction and 5.6 A along the equator. Here we show that the G- to F-actin conformational transition is a simple relative rotation of the two major domains by about 20 degrees. As a result of the domain rotation, the actin molecule in the filament is flat. The flat form is essential for the formation of stable, helical F-actin. Our F-actin structure model provides the basis for understanding actin polymerization as well as its molecular interactions with actin-binding proteins.

Recruitment Kinetics of Tropomyosin Tpm3.1 to Actin Filament Bundles in the Cytoskeleton Is Independent of Actin Filament Kinetics.

PubMed

Appaduray, Mark A; Masedunskas, Andrius; Bryce, Nicole S; Lucas, Christine A; Warren, Sean C; Timpson, Paul; Stear, Jeffrey H; Gunning, Peter W; Hardeman, Edna C

2016-01-01

The actin cytoskeleton is a dynamic network of filaments that is involved in virtually every cellular process. Most actin filaments in metazoa exist as a co-polymer of actin and tropomyosin (Tpm) and the function of an actin filament is primarily defined by the specific Tpm isoform associated with it. However, there is little information on the interdependence of these co-polymers during filament assembly and disassembly. We addressed this by investigating the recovery kinetics of fluorescently tagged isoform Tpm3.1 into actin filament bundles using FRAP analysis in cell culture and in vivo in rats using intracellular intravital microscopy, in the presence or absence of the actin-targeting drug jasplakinolide. The mobile fraction of Tpm3.1 is between 50% and 70% depending on whether the tag is at the C- or N-terminus and whether the analysis is in vivo or in cultured cells. We find that the continuous dynamic exchange of Tpm3.1 is not significantly impacted by jasplakinolide, unlike tagged actin. We conclude that tagged Tpm3.1 may be able to undergo exchange in actin filament bundles largely independent of the assembly and turnover of actin.

Liquid behavior of cross-linked actin bundles.

PubMed

Weirich, Kimberly L; Banerjee, Shiladitya; Dasbiswas, Kinjal; Witten, Thomas A; Vaikuntanathan, Suriyanarayanan; Gardel, Margaret L

2017-02-28

The actin cytoskeleton is a critical regulator of cytoplasmic architecture and mechanics, essential in a myriad of physiological processes. Here we demonstrate a liquid phase of actin filaments in the presence of the physiological cross-linker, filamin. Filamin condenses short actin filaments into spindle-shaped droplets, or tactoids, with shape dynamics consistent with a continuum model of anisotropic liquids. We find that cross-linker density controls the droplet shape and deformation timescales, consistent with a variable interfacial tension and viscosity. Near the liquid-solid transition, cross-linked actin bundles show behaviors reminiscent of fluid threads, including capillary instabilities and contraction. These data reveal a liquid droplet phase of actin, demixed from the surrounding solution and dominated by interfacial tension. These results suggest a mechanism to control organization, morphology, and dynamics of the actin cytoskeleton.

Molecular cloning of actin genes in Trichomonas vaginalis and phylogeny inferred from actin sequences.

PubMed

Bricheux, G; Brugerolle, G

1997-08-01

The parasitic protozoan Trichomonas vaginalis is known to contain the ubiquitous and highly conserved protein actin. A genomic library and a cDNA library have been screened to identify and clone the actin gene(s) of T. vaginalis. The nucleotide sequence of one gene and its flanking regions have been determined. The open reading frame encodes a protein of 376 amino acids. The sequence is not interrupted by any introns and the promoter could be represented by a 10 bp motif close to a consensus motif also found upstream of most sequenced T. vaginalis genes. The five different clones isolated from the cDNA library have similar sequences and encode three actin proteins differing only by one or two amino acids. A phylogenetic analysis of 31 actin sequences by distance matrix and parsimony methods, using centractin as outgroup, gives congruent trees with Parabasala branching above Diplomonadida.

Tropomyosin inhibits ADF/cofilin-dependent actin filament dynamics.

PubMed

Ono, Shoichiro; Ono, Kanako